Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction According to Polypharmacy Status.

BACKGROUND: Patients with heart failure (HF) have a high burden of multimorbidity, often necessitating numerous medications. There may be clinical concern about introducing another medication, especially among individuals with polypharmacy. OBJECTIVES: This study examined the efficacy and safety of addition of dapagliflozin according to the number of concomitant medications in HF with mildly reduced or preserved ejection fraction. METHODS: In this post hoc analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, 6,263 participants with symptomatic HF with left ventricular ejection fraction >40% were randomized to dapagliflozin or placebo. Baseline medication use (including vitamins and supplements) was collected. Efficacy and safety outcomes were assessed by medication use categories ("nonpolypharmacy": <5 medications; "polypharmacy": 5 to 9 medications; and "hyperpolypharmacy": ≥10 medications) and continuously. The primary outcome was worsening HF or cardiovascular death. RESULTS: Overall, 3,795 (60.6%) patients met polypharmacy and 1,886 (30.1%) met hyperpolypharmacy criteria. Higher numbers of medications were strongly associated with higher comorbidity burden and increased rates of the primary outcome. Compared with placebo, dapagliflozin similarly reduced the risk of the primary outcome irrespective of polypharmacy status (nonpolypharmacy HR: 0.88 [95% CI: 0.58-1.34]; polypharmacy HR: 0.88 [95% CI: 0.75-1.03]; hyperpolypharmacy HR: 0.73 [95% CI: 0.60-0.88]; Pinteraction = 0.30). Similarly, benefits with dapagliflozin were consistent across the spectrum of total medication use (Pinteraction = 0.06). Although adverse events increased with higher number of medications, they were not more frequent with dapagliflozin, regardless of polypharmacy status. CONCLUSIONS: In the DELIVER trial, dapagliflozin safely reduced worsening HF or cardiovascular death across a broad range of baseline medication use, including among individuals with polypharmacy (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).

[Update on diastolic heart failure]. / Update zur diastolisch bedingten Herzinsuffizienz.

In August 2021, an update of the European Society of Cardiology-Heart Failure Association guideline for the diagnosis and treatment of heart failure was released. To review the changes implied by current guidelines regarding the diagnosis and treatment of patients with heart failure and preserved left ventricular ejection fraction (HFpEF). The diagnosis of HFpEF requires the combined presence of clinical signs, left ventricular ejection fraction ≥ 50%, elevated natriuretic peptides, and elevated left ventricular filling pressure. If the diagnosis remains equivocal, a stress test is recommended. The targeted identification and treatment of comorbid conditions is key for a holistic therapeutic approach to HFpEF. Diuretics are recommended in congested patients with HFpEF in order to alleviate signs and symptoms. The treatment of diabetic patients with heart failure should include a sodium glucose co-transporter­2 (SGLT2) inhibitor. All patients with HFpEF should be enrolled in a multidisciplinary heart failure management program aiming to improve self-care strategies and offer participation in an exercise program. It was recently shown for the first time in a randomized trial that hard clinical endpoints could be reduced in patients with HFpEF using the SGLT2 inhibitor empagliflozin. It is expected that this finding will become part of updated treatment recommendations in the near future. Although challenging, the early diagnosis of HFpEF is key to averting the poor prognosis associated with this frequent condition. Multidisciplinary care and innovative pharmacologic and non-pharmacologic therapies, however, can improve quality of life, exercise tolerance, and prognosis.

Coenzyme Q10 in the Treatment of Heart Failure with Preserved Ejection Fraction: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in elderly people and is increasing in prevalence. No specific treatment for this condition exists. Coenzyme Q10 (CoQ10) is an essential cofactor for energy production, with reduced levels being noted in HF. Previous studies have suggested a possible role for CoQ10 in the treatment of HF. This study examined the effect of CoQ10 supplementation on diastolic function in HFpEF patients. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial including patients aged > 55 years presenting with New York Heart Association class II-IV heart failure symptoms and left ventricular ejection fraction > 50%, with impaired diastolic function. Echocardiography and levels of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed at baseline and following 4 months of CoQ10 or placebo supplementation. RESULTS: A total of 39 patients were enrolled-19 in the CoQ10 group and 20 in the placebo group. Baseline clinical characteristics were similar between groups, while compliance was high and also similar between the CoQ10 and placebo groups. There was no significant effect of treatment on indices of diastolic function (difference in the lateral E/e' ratio: -0.86 ± 6.57 in the CoQ10 group, +0.18 ± 3.76 in the placebo group; p = 0.561) or on serum NT-proBNP levels (- 72 pg/mL vs. - 42 pg/mL; p = 0.195). CONCLUSIONS: In this pilot trial in elderly patients with HFpEF, treatment with CoQ10 did not significantly affect echocardiographic indices of diastolic function and serum NT-proBNP levels. TRIAL REGISTRATION: This trial was registered in the US National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov identifier: NCT02779634).

Paediatric heart failure in Uyo A retrospective analysis

heart failure is a condition that continues to present challenges in management in our environment especially in its treatment and outcomes hence the aim of this study. Materials and Methods: A retrospective analysis of the case notes of all children who were diagnosed and managed for heart failure from January 2019 ­ October 2021 was undertaken. Data obtained included age, sex, presenting features, primary diagnosis, treatment modalities, duration of hospital stay and outcomes. Results: A total of 2226 children were admitted over the study period with 67 children diagnosed with heart failure giving a prevalence rate of 3% although only 47 case notes could be retrieved giving a case retrieval rate of 70%. There were 26 (55.3%) males and 21 (44.7%) females (M: F ratio1.2:1). Mean age of patients was 32.6 months (±52.23) with 28(59.6%) of them being infants. Bronchopneumonia was the commonest cause of heart failure 31 (65.9%) either singly or in combination with a cyanotic congenital heart disease followed by severe anemia in 14 (29.8%). Average duration of hospital stay was 6.9days (±5.08) and average cost of admission was N13,266. Twenty-three patients were discharged (48.9%), while 10 (21.3%) left against medical advice, 2 absconded (4.3%) while 12 (25.3%) died. Conclusion: Heart failure remains an important cause of morbidity and mortality in children in our environment arising from largely preventable causes. Urgent steps such as patient care giver education, immunization and screening for congenital heart disease are needed to reduce its effect on children in our environment

Improvement of Shen'ge formula on heart function in diastolic heart failure: A protocol for randomized, double-blind, placebo-controlled clinical study.

INTRODUCTION: Diastolic heart failure (DHF) is an important pathological type of heart failure, that involves multiple organ dysfunction and multiple complications. The prevalence of DHF is high, and effective treatments are lacking. Chinese herbs are an alternative therapy for DHF. Shen'ge formula (SGF) is a classical formula from which patients can benefit, but convincing evidence of its efficacy is lacking. Therefore, we designed this randomized controlled trial protocol. METHODS/DESIGN: This randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of SGF in the treatment of DHF. A total of 130 patients with DHF will be enrolled in the trial and treated with SGF granules or placebo for 12 weeks and followed up for 12 weeks. The primary outcome measurement will be to changes in plasma N-terminal brain natriuretic peptide precursor before versus after treatment, while the second primary outcome measurement will be changes in heart function before versus after treatment and the 12-week follow-up period. It will also include echocardiography, a cardiopulmonary exercise test, cardiac function grading, traditional Chinese medicine syndrome score, and the Minnesota Heart Failure Quality of Life Scale. Adverse events will be evaluated throughout the trial. DISCUSSION: The results of this trial will demonstrate whether SGF could alleviate symptoms, improve cardiac function, reduce readmission rates, and improve quality of life of patients with DHF. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000036533, registered on August 24, 2020.

Canola oil rich in oleic acid improves diastolic heart function in diet-induced obese rats.

Obesity is a leading cause of cardiovascular disease. It directly affects heart structure and function and contributes to heart failure. Diet is a major factor involved in the development of obesity along with genetic factors. We examined the effects of monounsaturated and polyunsaturated fatty acid-rich oils on cardiac structure and function in the diet-induced rodent model of obesity (DIO). Obese prone (OP) rats were fed a high-fat diet (HF; 55% of kcal) for 12 weeks; Sprague-Dawley rats fed commercial chow served as control. Echocardiography was performed to assess the cardiac structure and function in all rats at 12 weeks. OP rats fed the HF diet showed significant impairment in diastolic function compared to control rats. The HF diet containing high oleic canola oil significantly improved diastolic function of OP rats compared to the HF diet with lard. In conclusion, canola oil rich in oleic acid, when incorporated into an HF diet, prevents the development of diastolic dysfunction in DIO rats.

[Effect of Kanli Granule on Myocardial Mechanics in Pressure Overload Induced Diastolic Heart Failure Rats].

OBJECTIVE: To observe the effect of Kanli Granule (KG) on myocardial mechanics in pressure overload induced diastolic heart failure (DHF) rats. METHODS: Totally 60 male Wistar rats were divided into the sham-operation group, the model group, the KG group, and the Valsartan group according to random digit table, 15 in each group. The pressure overload induced DHF model was established in all groups except the sham-operation group using abdominal aortic constriction surgery. Totally 7 rats died after modeling (with the mortality of 10. 67%) , and the rest 53 finished the following test. Rats in the KG group were administered with KG extract (calculated as 6. 75 g crude drug/kg) by gastrogavage. Rats in the Valsartan group were administered with Valsartan (7.2 µg/g) by gastrogavage. Equal volume of double distilled water was administered to rats in the model group and the sham-operation group by gastrogavage. All rats were intervened for 32 weeks. The response of isolated heart papillary muscle tonus to isoprenaline (ISO) and adenylate cyclase (Forskolin) was respectively observed. The enhancement phenomenon after resting development force (DF) of isolated heart papillary muscle tonus, and changes of DF in different Ca²âº concentrations were observed. RESULTS: (1) In the ISO response test: Compared with the sham-operation group, the amplifications of DF, ±df/dt, -df/dt were obviously elevated in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously lowered in the KG group (P < 0.01), and the amplification of ±df/dt was also reduced in the Valsartan group (P < 0.01). (2) In the Forskolin response test: Compared with the sham-operation group, the amplifications of DF and ±df/dt obviously increased in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously reduced in the KG group (P < 0.01), and the amplification of DF was also reduced in the Valsartan group (P < 0.05). (3) In post-resting DF enhancement test: Compared with the sham-operation group, the amplification of DF showed gradually decreasing tendency along with prolonged resting time in the model group, and they were obviously lowered at all time points (P < 0.05). Compared with the model group, the amplification of DF was gradually increasing along with prolonged resting time in the KG group. The amplification of DF at post-resting 240 s was obviously larger in the KG group than in the model group (P < 0.05). The amplification of post-resting DF still showed gradually decreasing tendency along with prolonged resting time in the Valsartan group, with increased amplifications of DF at post-resting 60 s and 120 s (P < 0. 05) (4) The amplifications of DF in different Ca²âº concentrations: Compared with the sham-operation group, the amplifications of DF were significantly elevated in different Ca²âº concentrations (1.75, 3.5, 7.0 mmol/L ) (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in amplification of DF in different Ca²âº concentrations in the KG group (P > 0.05). The amplifications of DF in different Ca²âº concentrations were significantly reduced in the Valsartan group (P < 0.05). CONCLUSIONS: The ISO response and the Forskolin response were enhanced in isolated heart papillary muscle tonus of pressure overload induced DHF rats; enhanced post-resting DF was reduced; DF in different supra-physiologic levels of Ca²âº was still enhanced. KG could significantly improve excessive enhancement of pressure overload induced DHF rats in ISO response and Forskolin response, and improve enhancement of post-resting myocardium.

Effect of Kanli Granule on Myocardial Mechanics in Pressure Overload Induced Diastolic Heart Failure Rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Kanli Granule (KG) on myocardial mechanics in pressure overload induced diastolic heart failure (DHF) rats.</p><p><b>METHODS</b>Totally 60 male Wistar rats were divided into the sham-operation group, the model group, the KG group, and the Valsartan group according to random digit table, 15 in each group. The pressure overload induced DHF model was established in all groups except the sham-operation group using abdominal aortic constriction surgery. Totally 7 rats died after modeling (with the mortality of 10. 67%) , and the rest 53 finished the following test. Rats in the KG group were administered with KG extract (calculated as 6. 75 g crude drug/kg) by gastrogavage. Rats in the Valsartan group were administered with Valsartan (7.2 µg/g) by gastrogavage. Equal volume of double distilled water was administered to rats in the model group and the sham-operation group by gastrogavage. All rats were intervened for 32 weeks. The response of isolated heart papillary muscle tonus to isoprenaline (ISO) and adenylate cyclase (Forskolin) was respectively observed. The enhancement phenomenon after resting development force (DF) of isolated heart papillary muscle tonus, and changes of DF in different Ca²⁺ concentrations were observed.</p><p><b>RESULTS</b>(1) In the ISO response test: Compared with the sham-operation group, the amplifications of DF, ±df/dt, -df/dt were obviously elevated in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously lowered in the KG group (P < 0.01), and the amplification of ±df/dt was also reduced in the Valsartan group (P < 0.01). (2) In the Forskolin response test: Compared with the sham-operation group, the amplifications of DF and ±df/dt obviously increased in the model group (P < 0.05). Compared with the model group, the amplifications of DF and ±df/dt were obviously reduced in the KG group (P < 0.01), and the amplification of DF was also reduced in the Valsartan group (P < 0.05). (3) In post-resting DF enhancement test: Compared with the sham-operation group, the amplification of DF showed gradually decreasing tendency along with prolonged resting time in the model group, and they were obviously lowered at all time points (P < 0.05). Compared with the model group, the amplification of DF was gradually increasing along with prolonged resting time in the KG group. The amplification of DF at post-resting 240 s was obviously larger in the KG group than in the model group (P < 0.05). The amplification of post-resting DF still showed gradually decreasing tendency along with prolonged resting time in the Valsartan group, with increased amplifications of DF at post-resting 60 s and 120 s (P < 0. 05) (4) The amplifications of DF in different Ca²⁺ concentrations: Compared with the sham-operation group, the amplifications of DF were significantly elevated in different Ca²⁺ concentrations (1.75, 3.5, 7.0 mmol/L ) (P < 0.05, P < 0.01). Compared with the model group, there was no statistical difference in amplification of DF in different Ca²⁺ concentrations in the KG group (P > 0.05). The amplifications of DF in different Ca²⁺ concentrations were significantly reduced in the Valsartan group (P < 0.05).</p><p><b>CONCLUSIONS</b>The ISO response and the Forskolin response were enhanced in isolated heart papillary muscle tonus of pressure overload induced DHF rats; enhanced post-resting DF was reduced; DF in different supra-physiologic levels of Ca²⁺ was still enhanced. KG could significantly improve excessive enhancement of pressure overload induced DHF rats in ISO response and Forskolin response, and improve enhancement of post-resting myocardium.</p>

Myocardial energetics and ubiquinol in diastolic heart failure.

Diastolic heart failure, or heart failure with preserved ejection fraction, is a leading cause of morbidity and mortality. There are no current therapies effective in improving outcomes for these patients. The aim of this article is to review the literature and examine the role of coenzyme Q10 in heart failure with preserved ejection fraction related to mitochondrial synthesis of adenosine triphosphate and reactive oxygen species production. The study results reflect that myocardial energetics alters in diastolic heart failure and that there is defective energy metabolism and increased oxidative stress. Studies are emerging to evaluate coenzyme Q10 , particularly ubiquinol, as a supplemental treatment for heart-failure patients. In diastolic heart-failure patients, clinicians are beginning to use supplemental therapies to improve patient outcomes, and one promising complementary treatment to improve left ventricular diastolic function is ubiquinol. Additional studies are needed using large-scale randomized models to confirm if ubiquinol would be beneficial. Since ubiquinol is an antioxidant and is required for adenosine triphosphate production, clinicians and health scientists should be aware of the potential role of this supplement in the treatment of diastolic heart failure.

Vitamin D deficiency is associated with increased left ventricular mass and diastolic dysfunction in children with chronic kidney disease.

Cardiovascular disease currently is the leading cause of morbidity and mortality among patients with chronic kidney disease (CKD). Abnormalities in arterial compliance, increased left ventricular mass, and diastolic dysfunction are some of the recognized cardiovascular complications observed in these patients. This study explored the relationship between various parameters of calcium-phosphorus metabolism including 25-hydroxy vitamin D and cardiovascular structure and function in pediatric patients with CKD. This cross-sectional study was conducted using a cohort of 34 children with CKD who had no history of underlying congenital or structural cardiac disease. Two-dimensional echocardiography was used to measure the left ventricular mass index (LVMI), E/A ratio, E', E/E' ratio, and myocardial performance index (MPI). The augmentation index (AI), derived via radial artery tonometry, was used as an indirect measure of central aortic stiffness. Serum biochemical markers of calcium-phosphorus metabolism were simultaneously measured. Univariate analysis showed that LVMI correlated with 25-hydroxy vitamin D (r = -0.54; p < 0.05), systolic blood pressure (SBP) (r = 0.36; p < 0.05), and AI (r = 0.26; p < 0.05). Serum-intact parathyroid hormone (PTH) levels correlated with the E/E' ratio (r = 0.63; p < 0.05) and E' (r = -0.61; p < 0.05). Multiple regression analysis showed that 25-hydroxy vitamin D and SBP were independent predictors of increased LVMI and that PTH was an independent predictor of diastolic dysfunction. This is the first study investigating pediatric patients with CKD that suggests an etiology of nutritional vitamin D deficiency associated with increased left ventricular mass and diastolic dysfunction. The cardiovascular changes observed are not easily reversible. Hence, early preventive therapy with vitamin D supplementation is advocated.

Tetrahydrobiopterin improves diastolic dysfunction by reversing changes in myofilament properties.

Despite the increasing prevalence of heart failure with preserved left ventricular function, there are no specific treatments, partially because the mechanism of impaired relaxation is incompletely understood. Evidence indicates that cardiac relaxation may depend on nitric oxide (NO), generated by NO synthase (NOS) requiring the co-factor tetrahydrobiopterin (BH(4)). Recently, we reported that hypertension-induced diastolic dysfunction was accompanied by cardiac BH(4) depletion, NOS uncoupling, a depression in myofilament cross-bridge kinetics, and S-glutathionylation of myosin binding protein C (MyBP-C). We hypothesized that the mechanism by which BH(4) ameliorates diastolic dysfunction is by preventing glutathionylation of MyBP-C and thus reversing changes of myofilament properties that occur during diastolic dysfunction. We used the deoxycorticosterone acetate (DOCA)-salt mouse model, which demonstrates mild hypertension, myocardial oxidative stress, and diastolic dysfunction. Mice were divided into two groups that received control diet and two groups that received BH(4) supplement for 7days after developing diastolic dysfunction at post-operative day 11. Mice were assessed by echocardiography. Left ventricular papillary detergent-extracted fiber bundles were isolated for simultaneous determination of force and ATPase activity. Sarcomeric protein glutathionylation was assessed by immunoblotting. DOCA-salt mice exhibited diastolic dysfunction that was reversed after BH(4) treatment. Diastolic sarcomere length (DOCA-salt 1.70±0.01 vs. DOCA-salt+BH(4) 1.77±0.01µm, P<0.001) and relengthening (relaxation constant, τ, DOCA-salt 0.28±0.02 vs. DOCA-salt+BH(4) 0.08±0.01, P<0.001) were also restored to control by BH(4) treatment. pCa(50) for tension increased in DOCA-salt compared to sham but reverted to sham levels after BH(4) treatment. Maximum ATPase rate and tension cost (ΔATPase/ΔTension) decreased in DOCA-salt compared to sham, but increased after BH(4) treatment. Cardiac MyBP-C glutathionylation increased in DOCA-salt compared to sham, but decreased with BH(4) treatment. MyBP-C glutathionylation correlated with the presence of diastolic dysfunction. Our results suggest that by depressing S-glutathionylation of MyBP-C, BH(4) ameliorates diastolic dysfunction by reversing a decrease in cross-bridge turnover kinetics. These data provide evidence for modulation of cardiac relaxation by post-translational modification of myofilament proteins.

Suplementação de vitamina D na insuficiência cardíaca com fração de ejeção normal: impacto na qualidade de vida: estudo FITNESS / Vitamin D supplementation in normal ejection fraction heart: impact on quality of life: FITNESS study

Fundamentos: Estudos demonstram a importante prevalência do déficit de vitamina D (vit. D) em pacientes com insuficiência cardíaca com fração deejeção reduzida (ICFER). O déficit de vit. D se relaciona com a piora na qualidade de vida e redução do desempenho funcional. Com o envelhecimento, a insuficiência cardíaca com fração de ejeção normal (ICFEN) tornar-se-á o tipo de insuficiência cardíaca mais comum, com resultados referentes ao prognóstico semelhantes aos da ICFER. Apesar das evidências daação benéfica da vit. D no sistema cardiovascular em pacientes com ICFER, não há estudos clínicos que demonstrem a melhora morfofuncional cardiovascularcom a suplementação de vit.D em pacientes com ICFEN. Objetivo: Demonstrar a melhora da qualidade de vida e função diastólica em pacientes com ICFEN, após suplementação de vit. D. Métodos: E s t u d o p ro s p e c t i v o , d u p l o-c e g o randomizado, placebo controlado, envolvendo 40 pacientes com ICFEN e deficiência de vit. D (25OHD<30ng/mL), por 20 semanas de tratamento. Os pacientes receberão suplementação de 100.000UI decolecalciferol ou placebo no início do estudo e na 10ª semana, sob supervisão médica. Os pacientes serão avaliados por: testes funcionais (timed up and go test e 6 minute walk test), exames laboratoriais, questionário Minnesota Living with Heart Failure, eletrocardiograma e ecoDopplercardiograma, avaliando a função sistólica, a diastólica e o remodelamento ventricular no início doestudo, em 10 semanas e em 20 semanas. Conclusão: O estudo FITNESS avaliará o impacto morfofuncional cardiovascular e na qualidade de vida em 20 semanas na suplementação de colecalciferol em pacientes com ICFEN e déficit de vit. D.

Background: Studies have shown a significant prevalence of vitamin D (Vit. D) deficits in heart failure patients with reduced ejection fraction(HFREF), related to poorer quality of life andreductions in functional performance. With anaging population, heart failure with preserved ejection fraction (HFPEF) will become the most common type of heart failure (HF), with similar results for HFREF predictions. Despite evidence of the beneficial action of vit. D on the cardiovascular system in HFREF patients, there are no clinical s t u d i e s demo n s t r a t i n g c a rd i o v a s c u l a r morphofunctional improvement through vit.D supplementation in HFPEF patients. Objective: To demonstrate improvements in the quality of life and diastolic function for FPEF patients taking vit. D supplements. Methods: Prospective, double-blind, randomized, placebo-controlled study, with 40 patients with HFNEF and vit. D deficiency (25OHD <30ng/mL)for 20 weeks of treatment. Patients will receive supplements of 100,000IU of cholecalciferol (Vit. D3)or placebo at baseline and at 10 weeks under medical supervision. They will be assessed by: functional tests (timed up-and-go test and 6-minute walk test),laboratory examinations, the Minnesota Living with Heart Failure Questionnaire, electrocardiogram, evaluating systolic and diastolic functions and ventricular remodeling at baseline, and at 10 and 20weeks.Conclusion: The FITNESS study will evaluate cardiovascular morphofunctional impacts and effects on the quality of life during 20 weeks of cholecalciferol supplementation in HFPEF patients with vit. D deficits.

Heart failure, diastolic dysfunction and atrial fibrillation; mechanistic insight of a complex inter-relationship.

Atrial fibrillation (AF) and heart failure (HF) commonly coexist, and their co-presence is associated with adverse outcomes relating to thromboembolic events, HF progression, hospitalisation and death. Diastolic dysfunction (DD) is also frequently present in patients with HF and is an independent predictor of hospitalisation and mortality. The presence of DD is a strong predictor of incident AF in patients with HF. In this review, we provide mechanistic insight into pathophysiological processes that frequently promote the occurrence of AF, HF and DD and outline the yin-yang relationship between AF, DD and HF. More recently, invasive studies have also shown that asymptomatic paroxysmal atrial fibrillation (PAF) is a common phenomenon in HF patients. We examine complex inter-relationships between PAF, HF and DD and speculate upon the possible clinical influence of undiagnosed PAF in HF patients.

[Effect of Nuanxin Capsule on two rat models with heart failure].

OBJECTIVE: To observe the effects of Nuanxin Capsule (NC) on the rat models of heart failure induced by abdominal aorta constriction and adriamycin. METHODS: Rats were randomly divided into the following groups: model control group, low-dose and high-dose, and digoxin group. Meanwhile, the pseudo-operation and NC groups were seperately established. After treatment for 30 days, the heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal rate of increase and decrease in left ventricular pressure (+/- dp/dt), mean peripheral blood pressure (MBP) as well as levels of serum superoxide dismustase (SOD), malondialdeh-vde (MDA), cardiac index and heart size were measured. RESULTS: SBP, LVSP, +/- dp/dt and SOD activity increased,while LVEDP,serum MDA levels decreased in high and low-dose NC groups of two models. The heart rates also decreased, but the difference was insignificant (P>0.05, compared with those of model group). Besides, the heart rate,heart size and cardiac index, as well as serum Ang II levels also decreased. The differences were significant as compared with the digoxin group (P>0.05). The high-dose NC also significatly improved MBP and SOD (P<0.05 and P<0.01). CONCLUSION: Nuanxin Capsule has good therapeutic effects on the rats models of adriamycin and abdominal aorta constriction induced heart failure.

Therapeutic inhibition of miR-208a improves cardiac function and survival during heart failure.

BACKGROUND: Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. METHODS AND RESULTS: Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. CONCLUSIONS: These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression.

[Left ventricular function in patients with chronic heart failure. Practical aspects on echocardiographic timing and structured reports in the out-of-hospital ultrasound laboratory]. / La funzione ventricolare sinistra nel paziente con scompenso cardiaco cronico Spunti di riflessione sulla tempistica e sulla refertazione minima essenziale nell'ambulatorio di ecocardiografia del territorio.

This review addresses some practical aspects of Doppler echocardiography and how to perform it in outpatients with heart failure, in an attempt to make the diagnostic protocols more effective and less expensive for the national healthcare system. This problem comes from the relevant percentage of redundant echocardiographic exams that are irrelevant for the appropriate clinical management. The most important echocardiographic indices to be used for making diagnosis of left ventricular systolic and/or diastolic dysfunction are also discussed. In order to warrant the best quality of the healthcare system, correct timing, performance and structured reports are encouraged even in out-of-hospital echocardiography laboratories, driven by solid scientific knowledge and international guidelines.

Antifibrotic effects of ω-3 fatty acids in the heart: one possible treatment for diastolic heart failure.

Half of heart failure patients have diastolic heart failure, which has no effective treatments. Several studies indicate a role for ω-3 polyunsaturated fatty acids (PUFAs) in heart failure. Recent studies suggest that ω-3 PUFAs inhibit cardiac fibrosis and attenuate diastolic dysfunction. This opens up possible new avenues for treatment of diastolic heart failure. In this review, we focus on the antifibrotic effects of ω-3 PUFAs in heart and the underlying cellular and molecular mechanisms.