Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure characterized by left ventricular diastolic dysfunction with preserved ejection fraction. With the aging of the population and the increasing prevalence of metabolic diseases, such as hypertension, obesity and diabetes, the prevalence of HFpEF is increasing. Compared with heart failure with reduced ejection fraction (HFrEF), conventional anti-heart failure drugs failed to reduce the mortality in HFpEF due to the complex pathophysiological mechanism and multiple comorbidities of HFpEF. It is known that the main changes of cardiac structure of in HFpEF are cardiac hypertrophy, myocardial fibrosis and left ventricular hypertrophy, and HFpEF is commonly associated with obesity, diabetes, hypertension, renal dysfunction and other diseases, but how these comorbidities cause structural and functional damage to the heart is not completely clear. Recent studies have shown that immune inflammatory response plays a vital role in the progression of HFpEF. This review focuses on the latest research progress in the role of inflammation in the process of HFpEF and the potential application of anti-inflammatory therapy in HFpEF, hoping to provide new research ideas and theoretical basis for the clinical prevention and treatment in HFpEF.
Humans ; Heart Failure ; Stroke Volume/physiology* ; Hypertrophy, Left Ventricular/metabolism* ; Ventricular Dysfunction, Left/metabolism* ; Inflammation/complications* ; Obesity ; Hypertension

Sheng-Mai-San (SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia (CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days (nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle (LV) dysfunction and structure abnormalities. After administration of SMS (0.55, 1.1, and 5.5 g·kg(-1)·d(-1)) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors (Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.
Animals ; Antioxidants ; pharmacology ; therapeutic use ; Apoptosis ; Cardiomyopathies ; drug therapy ; etiology ; Caspase 3 ; metabolism ; Cytochromes c ; metabolism ; Disease Models, Animal ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart Ventricles ; drug effects ; pathology ; physiopathology ; Hypoxia ; Male ; Mice, Inbred ICR ; Mitochondria ; drug effects ; metabolism ; Myocardium ; pathology ; Oxygen ; metabolism ; Phytotherapy ; Qi ; Up-Regulation ; Ventricular Dysfunction, Left ; drug therapy ; etiology ; bcl-2-Associated X Protein ; metabolism

BACKGROUNDTagged magnetic resonance imaging (MRI) is the non-invasive golden standard to measure myocardial deformity. Tissue Doppler Imaging can be used to assess myocardial deformity, however, it has the limitation of angle-dependence. Our study aimed to compare left ventricular torsion and strains measured by velocity-vector imaging (VVI) using echocardiography (echo-VVI) and MRI (MRI-VVI), and to validate them against harmonic phase tagged MRI (HARP MRI).

METHODSA total number of 34 subjects (14 normal and 20 patients) were evaluated. Apical and basal image of left ventricular short axis view were acquired for measurements of apical and basal rotation, circumferential and radial strain using both echo-VVI and MRI-VVI. An apical four-chamber view was obtained for measuring the distance between the apical and basal levels.

RESULTSThe correlations of segmental rotations, circumferential and radial strains were high between echo-VVI and HARP MRI, while the agreement of apical rotation was poor. Left ventricular torsion showed much better correlation and agreement between echo-VVI and HARP MRI than apical rotation: the coefficient was 0.97, P < 0.001. The correlation between MRI-VVI and HARP MRI in quantifying rotational parameters and strains was similar with echo-VVI and HARP MRI. Echo-VVI could discriminate normal and dysfunctional ventricles on either hypertensive or dilated cardiomyopathy.

CONCLUSIONThe data from this study show that (1) it is feasible to quantify left ventricular torsion and myocardial strain using echo-VVI and MRI-VVI in normal subjects, patients with left ventricular global systolic dysfunction and segment systolic dysfunction; (2) the agreement among all mechanical parameters derived from echo-VVI, MRI-VVI, and HARP MRI remained with clinically acceptable ranges.

Adult ; Algorithms ; Echocardiography ; methods ; Female ; Heart Ventricles ; metabolism ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Ventricular Dysfunction, Left ; pathology

Cardiac resynchronization therapy (CRT) has been proven its value in adult patients with congestive heart failure of low ejection fraction and wide QRS duration. Contrast to adult patients, CRT has been rarely applied for young patients. We report on a 9-yr-old boy with progressive left ventricular (LV) dilatation and dysfunction following chronic VVI pacemaker therapy for congenital complete atrioventricular block associated with maternal anti-SSA/Ro and SSB/La antibody. His LV dysfunction was improved after epicardially established CRT.
Antibodies, Antinuclear/metabolism ; Atrioventricular Block/congenital/therapy ; Cardiac Pacing, Artificial/*adverse effects ; *Cardiac Resynchronization Therapy ; Child ; Chronic Disease ; Electrocardiography ; Heart Ventricles ; Humans ; Male ; Natriuretic Peptide, Brain/blood ; Sjogren's Syndrome/immunology ; Ventricular Dysfunction, Left/etiology/radiography/*therapy

AIMTo investigate the relationship between the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 and ECM accumulation in rat left ventricle in a mechanical unloaded heart model.

METHODS12-week-old male Lewis rats were subjected to abdominal heterotopic heart transplantation to achieve pressure and volume unloading(mechanical unloading). Age and sex matched in situ heart of Lewis rats were used as control. Collagen volume fraction(CVF) was analyzed by picrosiris-red staining plus polarized microscopy. MMP-2 and -9 gelatinolytic activity were measured by gelatin-zymography. mRNA level of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by real-time quantitative PCR. TIMP-1 and TIMP-2 protein level were measured by immunoblotting.

RESULTSMyocardial cross-sectional area of transplanted heart was significantly reduced, and accompanied by excessive ECM deposition (CVF 5.22% +/- 1.6% vs. 2.21% +/- 0.9%, P < 0.05) compared to in situ heart. MMP-2 and MMP-9 activity were significantly increased, as well as mRNA level of MMP-2, MMP-9, TIMP-1 and TIMP-2 compared to in situ heart. TIMP-1 and TIMP-2 protein level in mechanically unloaded heart were significantly upregulated compared to in situ heart, especially for TIMP-1.

CONCLUSIONMechanical unloading of left ventricle may lead to excessive ECM deposition, accompanied by imbalance between MMPs and TIMPs system, especially the upregulation of TIMPs.

Animals ; Extracellular Matrix ; metabolism ; Gelatinases ; metabolism ; Heart Transplantation ; physiology ; Heart-Assist Devices ; Male ; Matrix Metalloproteinases ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Rats, Inbred Lew ; Tissue Inhibitor of Metalloproteinases ; metabolism ; Transplantation, Heterotopic ; physiology ; Ventricular Dysfunction, Left ; metabolism

The exact pathogenesis of transient mid- and basal ventricular ballooning, a new variant of transient left ventricular (LV) ballooning, remains unknown. We report two cases of transient mid- and basal ventricular ballooning associated with catecholamines. These cases suggest that catecholamine-mediated myocardial dysfunction might be a potential mechanism of this syndrome.
Adult ; Cardiomyopathies/pathology ; Catecholamines/*metabolism ; Coronary Vessels/pathology ; Heart Catheterization ; Heart Ventricles/pathology ; Humans ; Male ; Middle Aged ; Myocardial Contraction ; Myocardium/pathology ; Syndrome ; Tomography, X-Ray Computed/methods ; Ventricular Dysfunction, Left/diagnosis/*physiopathology

OBJECTIVETo observe the effects of heat shock protein 27 (Hsp27) overexpression on doxorubicin (Dox) induced mortality and cardiac dysfunction in a transgenic (TG) mouse model.

METHODSA linear DNA constituted of alpha-myosin heavy chain (alpha-MHC) promoter, human Hsp27cDNA and poly A was microinjected into fertilized eggs to generate transgenic mice and mice containing the transgene were identified by polymerase chain reaction and independent transgenic lines were established. Following successful transmission, tissues including heart, lung, liver, brain, skeleton muscle, spleen and kidney were screened by Western blot to confirm the cardiac specific expression of the transgene. TG and wild type littermates (WT) received a single dosage of Dox injection (25 mg/kg IP) or saline injection and observed for 5 days. Mice mortality was noticed and left ventricular (LV) hemodynamics were measured at day 5 in surviving mice. Cardiomyocyte apoptosis was evaluated by TUNEL assay at day 3 post Dox or saline injections in a separate group.

RESULTSThree independent transgenic lines were generated, and all of them expressed cardiac specific Hsp27. Five days mortality was significantly reduced in TG group than that in WT group post Dox (P < 0.01), Dox induced cardiac dysfunction and cardiomyocyte apoptosis were also significantly attenuated in TG mice compared to WT mice (P < 0.05).

CONCLUSIONOverexpression of Hsp27 reduced mortality, attenuated left ventricular dysfunction and cardiomyocyte apoptosis induced by Dox in a transgenic mouse model.

Animals ; Apoptosis ; Disease Models, Animal ; Doxorubicin ; HSP27 Heat-Shock Proteins ; metabolism ; Heart Failure ; blood ; metabolism ; pathology ; Humans ; Mice ; Mice, Transgenic ; Myocytes, Cardiac ; cytology ; Oxidative Stress ; Ventricular Dysfunction, Left ; metabolism

OBJECTIVESVentricular remodeling is an important pathologic progress in almost all end stage heart failure (HF), and it is characterized by ventricular thickening and cardiac fibrosis with poor prognosis. The connective tissue growth factor (CTGF), a new growth factor with multi-function, has an important role in fibrosis of tissue and organs. It has been demonstrated that angiotensin-converting enzyme inhibitor (ACEI) can prevent the development of cardiomyocyte from remodeling and improve cardiac function. Researchers try to test the hypothesis that cardiac function improvement attributable to ACEI is associated with inhibiting expression of CTGF in patients with HF. The aim of this study was to observe changes in CTGF expression in cardiomyocyte of young rats with HF and effect of benazepril on CTGF.

METHODSThe animal model of HF was established by constriction of abdominal aorta. Five weeks old rats were randomly divided into 3 groups after 6 weeks of operation: (1) HF group without treatment (n = 15); (2) HF group where rats were treated with benazepril (n = 15); (3) sham-operated group (n = 15) where rats were administered benazepril through direct gastric gavage. After 4 weeks of treatment, the high frequency ultrasound was performed. The expression of CTGF was detected by immunohistochemistry and semi-quantative reverse transcription-polymerase chain reaction.

RESULTSCompared with the sham-operated group, left ventricular diastolic dimension (LVEDD), left ventricular systolic dimension (LVESD), interventricular septal thickness at end-diastole (IVSTd), interventricular septal thickness at end-systole (IVSTs), left ventricular posterior wall thickness at end-diastole (LVPWTd), left ventricular posterior wall thickness at end-systole (LVPWTs), left ventricular relative weight (LVRW), and right ventricular relative weight (RVRW) were all increased (P < 0.01), but ejection fraction (EF) and fractional shortening (FS) were decreased (P < 0.01). CTGF positive cells and expression of CTGF mRNA (0.609 +/- 0.065 vs 0.117 +/- 0.011, P < 0.01) were increased in HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were all decreased (P < 0.01), but FS and EF were increased (P < 0.01) in cases of HF treated with benazepril when compared with HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were higher (P < 0.01), EF and FS were lower (P < 0.01), CTGF positive cells and expression of CTGF mRNA were higher (P < 0.01) in HF group treated with benazepril than those of sham-operated group.

CONCLUSIONThe expression of CTGF was increased in the cardiomyocyte of young rats with HF and benazepril could prevent left ventricular from remodeling partly and improve cardiac function by inhibiting the expression of CTGF in cardiomyocyte in cases of HF.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Benzazepines ; pharmacology ; Connective Tissue Growth Factor ; metabolism ; Disease Models, Animal ; Heart Failure ; diagnostic imaging ; drug therapy ; metabolism ; physiopathology ; Immunohistochemistry ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; RNA, Messenger ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Ultrasonography ; Ventricular Dysfunction, Left ; diagnostic imaging ; drug therapy ; physiopathology ; Ventricular Remodeling ; drug effects

The potential for recovery of left ventricular dysfunction after myocardial revascularization represents a practical clinical definition for myocardial viability. The evaluation of viable myocardium in patients with severe global left ventricular dysfunction due to coronary artery disease and with regional dysfunction after acute myocardial infarction is an important issue whether left ventricular dysfunction may be reversible or irreversible after therapy. If the dysfunction is due to stunning or hibernation, functional improvement is observed. but stunned myocardium may recover of dysfunction with no revascularization. Hibernation is chronic process due to chronic reduction in the resting myocardial blood flow. There are two types of myocardial hibernation: "functional hibernation" with preserved contractile reserve and "structural hibernation" without contractile reserve in segments with preserved glucose metabolism. This review focus on the application of F-18 FDG and other radionuclides to evaluate myocardial viability. In addition the factors influencing predictive value of FDG imaging for evaluating viability and the different criteria for viability are also reviewed.
Coronary Artery Disease ; Glucose ; Hibernation ; Humans ; Metabolism ; Myocardial Infarction ; Myocardial Revascularization ; Myocardial Stunning ; Myocardium ; Radioisotopes ; Ventricular Dysfunction, Left

We compared rest perfusion PET with redistribution perfusion SPECT to investigate the concordant rate between PET and SPECT images and analyze the discordant pattern. MATERIALS AND METHODS: Rest N-13 ammonia and F-18 FDG PET were performed on 18 patients with old myocardial infarction and left ventricular dysfunction whose dipyridamole - 4hr redistribution Tl-201 SPECT showed one or more severe fixed defects. Regional perfusion and metabolism were evaluated visually and quantitatively with 5-segment myocardial model. RESULTS: There were high concordant rate in uptake pattern (80/90 segments, 88.9%) and high correlation coefficient on quantitative analysis (R=0.81, p< 0.001) between redistrubution Tl-201 SPECT and N-13 ammonia PET images. Nine of 18 patients had SPECT-PET concordant pattern (Group I). Ten segments (9 in inferior wall, 1 in apex) from the remaining 9 patients showed SPECT-PET discordant pattern with abnormal Tl-201 defect and near normal N-13 ammonia uptake (Group II). The diastolic and systolic left ventricular dimensions were significantly increased in Group II compared to those of Group I. When attenuation uncorrected N-13 ammonia PET images were reconstructed in Group II, it resulted in PET images with severe inferior wall defects nearly identical to those seen in redistribution Tl-201 SPECT images. CONCLUSION: Redistribution Tl-201 SPECT images showed high concordant rate and correlation with rest N-13 ammonia PET images. Most of discordant segments had fixed thallium defects in inferior wall with nearly normal N-13 ammonia uptake, which may result from severe left ventricular dilatation and attenuation by the left hemidiaphragm and cardiac blood pool.
Ammonia* ; Dilatation ; Dipyridamole ; Humans ; Metabolism ; Myocardial Infarction* ; Perfusion ; Thallium ; Tomography, Emission-Computed, Single-Photon* ; Ventricular Dysfunction, Left*