Effect of dapagliflozin on left ventricular structure and function in patients with non-ischemic dilated cardiomyopathy: An observational study.

Non-ischemic dilated cardiomyopathy (NIDCM) is characterized by left ventricular dilatation and contractile dysfunction with severe morbidity and mortality. Sodium glucose cotransporter type 2 (SGLT2) inhibitors significantly reduce cardiovascular events for heart failure patients. We performed to investigate the impact of combined administration of SGLT2 inhibitors on cardiac structure and function in NIDCM patients undergoing conventional therapy. A total of 50 newly diagnosed NIDCM patients received conventional medical therapy, with 23 receiving dapagliflozin 10mg/day in addition (SGLT2i group) and the remaining 27 only receiving conventional therapy (non-SGLT2i group). After 12 months outpatient follow-up, NIDCM patients treated with conventional therapy alone showed a significant reduction of left ventricular end-diastolic dimensions (LVEDd), left ventricular end-systolic dimensions (LVESd), left ventricular end-diastolic volumes (LVEDV), left ventricular end-systolic volumes (LVESV), left ventricular end-diastolic volume index (LVEDVi) and left ventricular end-systolic volume index (LVESVi), while an increase in fractional shortening (FS) and left ventricular ejection fraction (LVEF). Patients receiving dapagliflozin combined with conventional treatment also demonstrated a significant reduction in left ventricular dimensions and volumes, and a marked increase in cardiac function. In non-SGLT2i groups, the % change in LVEDd, LVESd, LVEDV, LVESV, LVEDVi, LVESVi, FS and LVEF was -2.8%, -4.6%, -6.2%, -10.1%, -6.1%, -10.1%, +9.7%, +11%. A greater absolute % fall in left ventricular volume in SGLT2i groups compared to non-SGLT2i groups resulted in a significant improvement in cardiac function. The results showed that SGLT2i combined with conventional therapy has a better beneficial effect on left ventricular volumes and cardiac function in NIDCM patients.

Comparative Efficacy of Different Drugs for the Treatment of Dilated Cardiomyopathy: A Systematic Review and Network Meta-analysis.

BACKGROUND AND OBJECTIVE: At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis. METHODS: The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis. RESULTS: There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR). CONCLUSION: A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.

Danicamtiv Increases Myosin Recruitment and Alters Cross-Bridge Cycling in Cardiac Muscle.

BACKGROUND: Modulating myosin function is a novel therapeutic approach in patients with cardiomyopathy. Danicamtiv is a novel myosin activator with promising preclinical data that is currently in clinical trials. While it is known that danicamtiv increases force and cardiomyocyte contractility without affecting calcium levels, detailed mechanistic studies regarding its mode of action are lacking. METHODS: Permeabilized porcine cardiac tissue and myofibrils were used for X-ray diffraction and mechanical measurements. A mouse model of genetic dilated cardiomyopathy was used to evaluate the ability of danicamtiv to correct the contractile deficit. RESULTS: Danicamtiv increased force and calcium sensitivity via increasing the number of myosins in the ON state and slowing cross-bridge turnover. Our detailed analysis showed that inhibition of ADP release results in decreased cross-bridge turnover with cross bridges staying attached longer and prolonging myofibril relaxation. Danicamtiv corrected decreased calcium sensitivity in demembranated tissue, abnormal twitch magnitude and kinetics in intact cardiac tissue, and reduced ejection fraction in the whole organ. CONCLUSIONS: As demonstrated by the detailed studies of Danicamtiv, increasing myosin recruitment and altering cross-bridge cycling are 2 mechanisms to increase force and calcium sensitivity in cardiac muscle. Myosin activators such as Danicamtiv can treat the causative hypocontractile phenotype in genetic dilated cardiomyopathy.

MANAGEMENT OF SUSPECTED DILATED CARDIOMYOPATHY WITH PIMOBENDAN IN TWO LEOPARD SHARKS (TRIAKIS SEMIFASCIATA).

Two adult male leopard sharks (Triakis semifasciata) under managed care were diagnosed with suspected dilated cardiomyopathy. Clinical signs included lethargy, inappetence, and regurgitation. On cardiac ultrasound, fractional shortening was 14% and 10%, respectively (versus 21%-31% in four healthy conspecifics). Ventricular end-diastolic diameter to body weight ratio was 1.72 cm/kg in Case 1 (versus 0.52-1.24 cm/kg in four conspecifics). These results collectively suggested a dilated cardiomyopathy. Treatment was implemented with oral pimobendan at 0.3 mg/kg q48h for 1 mon. The pimobendan dose was increased to 0.5 mg/kg 3/wk, following plasmatic dosage of pimobendan and its metabolite. After 3 mon, fractional shortening increased to 38% and 20%, respectively, sharks regained a normal appetite, and body weight increased by 50% in one individual. After 2 yr, both individuals remained clinically normal, and no adverse effect was noted with pimobendan administration. Pimobendan plasma concentration suggested that this medication was well absorbed in this species.

Clinical Profile, Treatment, and Prognosis of Left Ventricular Thrombus in Dilated Cardiomyopathy.

Despite the emerging prevalence of left ventricular (LV) thrombus in dilated cardiomyopathy (DCM), clinical characteristics, management, and disease prognosis are poorly studied. We aim to assess the efficacy/safety profile of direct oral anticoagulants (DOACs) compared to warfarin by evaluating thrombus evolution, risk for stroke and systemic embolism (SSE), heart failure (HF) rehospitalization, all-cause mortality, and major adverse cardiovascular events (MACEs), and determine the impact of thrombus evolution on adverse events. We performed a historical cohort study of patients with a primary diagnosis of DCM and LV thrombus. Relationships between anticoagulants and thrombus resolution were analyzed with the Kaplan-Meier method and Cox regression. Associations between longitudinal thrombus evolution and adverse event hazard were measured with joint modeling. Among 122 patients included, 58.0% were prescribed warfarin, and 42.0% DOACs. Complete thrombus resolution at 90-day-after-index and 180-day-after-index was observed in 93 and 111 patients, with no difference in cumulative resolution between DOACs and warfarin. During a median follow-up of 12.5 months, MACE, all-cause death, SSE, and HF rehospitalization occurred in 42.6%, 27.9%, 4.1%, and 13.9% of patients, comparable in warfarin and DOACs groups. Thrombus persistence was associated with a higher risk of HF rehospitalization. Thrombus progression was associated with poor prognosis, with per unit increment in square-root-transformed thrombus-area resulting in a 1.0691-fold increase in MACE risk and a 1.0546-fold increase in death risk. This study suggests that in DCM patients with LV thrombus, DOACs were comparable to warfarin in thrombus resolution and safety profile. Thrombus persistence or progression was associated with an increased risk of HF rehospitalization, MACE, and mortality.

Evaluation of the pharmacotherapeutic impact on contractility recovery in patients with newly diagnosed, acute onset dilated cardiomyopathy.

In patients with acute onset dilated cardiomyopathy (DCM) an improvement of left ventricular ejection fraction (LVEF) can occur as an effect of complex therapy. The aim of the study was to evaluate a pharmacotherapeutic impact on LVEF recovery in newly diagnosed DCM heart failure (HF) patients. A total of 2436 patients hospitalized due to acute decompensated HF were retrospectively analyzed. Finally, 24 patients with newly diagnosed DCM (51.4 ±â€…16.3 years, New York Heart Association 2.3 ±â€…0.7, LVEF 25 ±â€…10%) were observed (13.4 ±â€…16.0 months) in terms of the result of complex therapy. Patients were divided according to LVEF improvement on follow-up echocardiography: "recovery group" (LVEF improvement > 5%; n = 13) and "nonrecovery group" (∆LVEF ≤ 5%; n = 11). Evaluation of baseline parameters showed lower LVEF (19 ±â€…6 vs 31 ±â€…10%; P = .0048) and lower incidence of arterial hypertension (27% vs 73%; P = .043) in "recovery" group. After follow-up period LVEF was similar in both groups; however, significant LVEF improvement was demonstrated only in the "recovery group" (19 ±â€…6% to 34 ±â€…8%; P < .001). Only the "recovery group" showed significant HF symptoms reduction (New York Heart Association class: 2.5 ±â€…0.7 to 1.6 ±â€…0.6; P = .003). The "recovery group" had prescribed higher doses of loop diuretic (equivalent dose of furosemidum: 80 ±â€…38 mg vs 43 ±â€…24 mg; P = .025). Despite optimal therapy, significant LVEF improvement is observed only in the half of the patients with newly diagnosed DCM with HF with reduced EF. Prescription of higher doses of loop diuretics may have positive effect on the reduction of symptoms in newly diagnosed DCM HF patients. Lack of other risk factors such as arterial hypertension may increase the chance of LVEF recovery.

Long-term effectiveness of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene: a plain language summary.

WHAT IS THIS PLAIN LANGUAGE SUMMARY ABOUT?: This summary explains the results of a long-term extension study on the effects of a specific medicine. A long-term extension study allows people who have already completed a research study to continue taking treatment. Researchers can then look at how a treatment works over a long period of time. This extension study looked at the effects of a medicine called ARRY-371797 (also known as PF-07265803) in people with dilated cardiomyopathy (DCM for short) caused by a faulty lamin A/C gene (also known as the LMNA gene). This condition is called LMNA-related DCM. In people with LMNA-related DCM, the heart muscle becomes thinner and weaker than normal. This can lead to heart failure, where the heart is unable to pump enough blood around the body. The extension study allowed people who had completed an earlier 48-week study to continue taking ARRY-371797 for another 96 weeks (around 22 months). WHAT WERE THE RESULTS OF THE EXTENSION STUDY?: 8 people joined the extension study and continued with the dose of ARRY-371797 that they had taken in the first study. This means that people could have taken ARRY-371797 continuously for up to 144 weeks (around 2 years and 9 months). Using the 6-minute walk test (6MWT for short), researchers regularly checked people taking ARRY-371797 to see how far they could walk. Throughout the extension study, people were able to walk further than they could before they started taking ARRY-371797. This suggests that people could maintain the improvements in their ability to do daily activities with long-term ARRY-371797 treatment. Researchers also looked at how severe people's heart failure was by using a test that measures levels of a biomarker called NT-proBNP. A biomarker is something found in the body that can be measured to indicate the extent of a disease. Throughout this study, the levels of NT-proBNP in people's blood was lower than before they started taking ARRY-371797. This suggests that they maintained stable heart function. Using the Kansas City Cardiomyopathy Questionnaire (KCCQ for short), researchers asked people about their quality of life, and if they experienced any side effects. A side effect is something that people feel while taking a treatment. Researchers evaluate if a side effect is related to the treatment or not. Some improvement in KCCQ response during the study was seen, although results were varied. There were no serious side effects that were considered related to treatment with ARRY-371797. WHAT DO THE RESULTS OF THE EXTENSION STUDY MEAN?: Researchers found that the improvements in functional capacity and heart function seen with ARRY-371797 treatment in the original study were maintained with long-term treatment. Larger studies are needed to determine if ARRY-371797 could be an effective treatment for people with LMNA-related DCM. One such study (called REALM-DCM) was started in 2018 but ended early, as it was unlikely to show a clear treatment benefit of ARRY-371797. Phase 2 long-term extension study (NCT02351856) Phase 2 study (NCT02057341) Phase 3 REALM-DCM study (NCT03439514).

Long-term milrinone therapy in children with dilated cardiomyopathy.

AIM: The aim of this study was to assess the safety and efficacy of long-term milrinone therapy in children with acute decompensated heart failure due to dilated cardiomyopathy (DCM). METHODS: A single-centre retrospective study of all children ≤18 years with acute decompensated heart failure and DCM who received continuous long-term (≥7 consecutive days) intravenous milrinone between January 2008 and January 2022. RESULTS: The 47 patients had a median age of 3.3 months [interquartile range (IQR) 1.0-18.1], weight of 5.7 kg [IQR 4.3-10.1] and fractional shortening of 11.9% [±4.7]. Idiopathic DCM (n = 19) and myocarditis (n = 18) were the most common diagnoses. The median milrinone infusion duration was 27 days [IQR 10-50, range 7-290]. No adverse events necessitated milrinone termination. Nine patients required mechanical circulatory support. Median follow-up was 4.2 years [IQR 2.7-8.6]. On initial admission, four patients died, six were transplanted and 79% [37/47] were discharged home. The 18 readmissions resulted in five more deaths and four transplantations. Cardiac function recovered in 60% [28/47], as measured by normalised fractional shortening. CONCLUSION: Long-term intravenous milrinone is safe and effective in paediatric acute decompensated DCM. Combined with conventional heart failure therapies, it can act as a bridge to recovery and thereby potentially reduce the need for mechanical support or heart transplantation.

Nationwide Temporal Trends in Clinical Characteristics and Treatment of Dilated Cardiomyopathy From 2003 to 2013 in Japan　- A Report From Clinical Personal Records.

BACKGROUND: Little is known about nationwide temporal trends in the clinical characteristics and treatment of dilated cardiomyopathy (DCM) in Japan.Methods and Results: We collected data regarding demographics, echocardiography, and treatment of DCM between 2003 to 2013 from Clinical Personal Records, a national registry organized by the Japanese Ministry of Health, Labour, and Welfare. Among the 40,794 DCM patients screened, 27,702 with left ventricular ejection fraction (LVEF) <50% and age ≥18 years were enrolled in this study and divided into 3 groups according to registration year: Group 1, 2003-2005 (10,006 patients); Group 2, 2006-2010 (11,252 patients); and Group 3, 2011-2013 (6,444 patients). Over time, there were decreases in age at registration (mean [±SD] 58.6±13.0 vs. 56.8±13.8 vs. 56.2±13.8 years; P<0.001) and LVEF (33.5±10.0% vs. 31.1±9.9% vs. 29.2± 9.7%; P<0.001), and an increase in patients with New York Heart Association Class III-IV (28.2% vs. 35.2% vs. 41.0%; P<0.001). The use of ß-blockers (59.1% vs. 79.3% vs. 87.8%; P<0.001) and mineralocorticoid receptor antagonists (30.6% vs. 35.8% vs. 39.7%; P<0.001) increased over time. In multivariate analysis, male sex, systolic blood pressure, chronic kidney disease, hemoglobin, and registration year were positively associated, whereas age and LVEF were negatively associated, with ß-blocker prescription. CONCLUSIONS: Although the clinical characteristics of DCM changed, the implementation of optimal medical therapy for DCM increased from 2003 to 2013 in Japan.

A Comprehensive Review of Dilated Cardiomyopathy in Pre-clinical Animal Models in Addition to Herbal Treatment Options and Multi-modality Imaging Strategies.

Dilated cardiomyopathy (DCM) is distinguished by ventricular chamber expansion, systolic dysfunction, and normal left ventricular (LV) wall thickness, and is mainly caused due to genetic or environmental factors; however, its aetiology is undetermined in the majority of patients. The focus of this work is on pathogenesis, small animal models, as well as the herbal medicinal approach, and the most recent advances in imaging modalities for patients with dilated cardiomyopathy. Several small animal models have been proposed over the last few years to mimic various pathomechanisms that contribute to dilated cardiomyopathy. Surgical procedures, gene mutations, and drug therapies are all characteristic features of these models. The pros and cons, including heart failure stimulation of extensively established small animal models for dilated cardiomyopathy, are illustrated, as these models tend to procure key insights and contribute to the development of innovative treatment techniques for patients. Traditional medicinal plants used as treatment in these models are also discussed, along with contemporary developments in herbal therapies. In the last few decades, accurate diagnosis, proper recognition of the underlying disease, specific risk stratification, and forecasting of clinical outcome, have indeed improved the health of DCM patients. Cardiac magnetic resonance (CMR) is the bullion criterion for assessing ventricular volume and ejection fraction in a reliable and consistent direction. Other technologies, like strain analysis and 3D echocardiography, have enhanced this technique's predictive and therapeutic potential. Nuclear imaging potentially helps doctors pinpoint the causative factors of left ventricular dysfunction, as with cardiac sarcoidosis and amyloidosis.

Dapagliflozin protects against dilated cardiomyopathy progression by targeting NLRP3 inflammasome activation.

Dilated cardiomyopathy (DCM) is the major cause of heart failure and has a poor prognosis. The accumulating evidence points to an essential role of the inflammatory component in the process of DCM. Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are widely used to treat heart failure patients due to their cardiac benefits. However, their role in DCM remains unclear. We used the doxorubicin (Dox)-induced DCM model for our study. The SGLT2 inhibitor dapagliflozin (Dapa) improved cardiac function in mice treated with doxorubicin and attenuated the activation of the nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome pathway and the expression of inflammatory factors. In addition, dapagliflozin suppresses NLRP3 activation by decreasing p38-dependent toll-like receptor 4 (TLR4) expression. In our study, dagliflozin improves cardiac function in DCM by inhibiting the activity of the NLRP3 inflammasome.

Efficacy and safety evaluation of Shenmai injections for dilated cardiomyopathy: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Shenmai Injection (SMI), a Chinese herbal injection, is widely used in China for the adjuvant treatment of patients with dilated cardiomyopathy (DCM), yet its clinical efficacy and safety remain controversial. PURPOSE: The aim of this study was to systematically evaluate the efficacy and safety of SMI in the treatment of DCM. METHODS: Randomised controlled trials (RCTs) of SMI in the treatment of DCM were searched for and collected from the PubMed, EMBASE, Cochrane Library, SinoMed, Wan Fang, CNKI, and VIP databases between the dates of establishment of each database and July 1, 2022. The methodological quality of the included studies was assessed, while the risk of bias was based on the Cochrane Collaboration tool. All data were analysed using the R software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to rate the quality of the evidence. RESULTS: In total, 16 RCTs, including 1,455 participants, were examined in this study. Evidence showed that the combination of SMI treatment and conventional treatment appears to significantly increase the clinical efficacy rate (OR=3.65, 95%CI (2.52, 5.28), p < 0.01), improve cardiac function (e.g. increase left ventricular ejection fraction (LVEF) (MD=5.31, 95%CI (4.21, 6.40), p < 0.01), decrease left ventricular end-diastolic dimension (LVEDD) (MD=-4.57, 95% CI (-7.10, -2.04); p < 0.01) and left ventricular end-systolic diameter (LVESD) (MD=-2.46, 95% CI (-3.60, -1.33); p < 0.01), decrease brain natriuretic peptide (BNP) (MD=-215.85, 95% CI (-241.61, -190.10); p < 0.01) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (MD=-504.42, 95% CI (-687.73, -321.10); p < 0.01), and increase 6-min walk distance (6MWD) (MD=114.08, 95% CI (42.32, 185.85); p < 0.01).In addition, no serious adverse effects associated with SMI were observed during the study period, thus suggesting that SMI is safe. However, the quality of evidence for these results was rated as "very low" to "low", mainly due to the poor methodological quality of the included RCTs, the small sample size, the high heterogeneity, and potential publication bias. CONCLUSION: In the present work, we provide evidence that combined SMI therapy is beneficial and safe for improving cardiac function in patients with DCM. However, due to limitations posed by the low methodological quality of the included trials, more rigorous and high-quality RCTs are needed to provide solid evidence.

Plain Language Summary of Publication of the safety and efficacy of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene.

WHAT IS THIS PLAIN LANGUAGE SUMMARY ABOUT?: This plain language summary describes the results of a study looking at the effects of a medicine called ARRY-371797 (also known as PF-07265803) in people with dilated cardiomyopathy (DCM for short) caused by a faulty LMNA gene. This condition is called LMNA-related DCM. DCM happens when the heart becomes bigger and weaker than normal, impacting functional capacity and leading to symptoms of heart failure. This means the heart is not able to pump blood around the body as easily, and people are unable to do as much in their daily lives (like getting dressed and going shopping). People may inherit a faulty LMNA gene from one of their parents, or a faulty LMNA gene may develop when mistakes happen during cell growth and replication. ARRY-371797 targets a specific mechanism in the body that can lead to heart problems in people with a faulty LMNA gene. As ARRY-371797 is not currently approved for use outside of clinical trials, it doesn't currently have an easily recognizable trade name. WHAT WERE THE RESULTS?: 12 American people (average age 50 years) with LMNA-related DCM took part in the study and received 400 mg or 100 mg of ARRY-371797 twice daily for 48 weeks. People knew which dose of ARRY-371797 they were taking. People were checked after 4, 12, 24, 36 and 48 weeks of taking ARRY-371797 to see how far they could walk in the 6-minute walk test (6MWT for short). The level of NT-proBNP in their blood was also measured. NT-proBNP is a biomarker used to measure the severity of heart failure. A biomarker is something found in the body that can be measured to indicate the extent of a disease. -After taking ARRY-371797 for 12 weeks, people were able to walk further in the 6MWT and had lower levels of NT-proBNP in their blood. This suggests improvement in functional capacity (exercise tolerance) and heart function. Researchers also asked people about their quality of life using the Kansas City Cardiomyopathy Questionnaire (KCCQ for short), and looked for any side effects. -Researchers saw some improvement in KCCQ scores. -Researchers saw no major side effects that they considered to be related to ARRY-371797 treatment. A side effect is something that people feel was caused by a medicine or treatment. Overall, this study showed that people with LMNA-related DCM who took ARRY-371797 had improved functional capacity (exercise tolerance), improved heart function, and improved quality of life. Phase 2 study (NCT02057341) Phase 2 long-term extension study (NCT02351856) Phase 3 REALM-DCM study (NCT03439514).

Efficacy and Safety of ARRY-371797 in LMNA-Related Dilated Cardiomyopathy: A Phase 2 Study.

BACKGROUND: Lamin A/C gene (LMNA)-related dilated cardiomyopathy is a serious and life-threatening condition with a high unmet medical need. This phase 2 study assessed the effects of the oral selective p38 mitogen-activated protein kinase inhibitor ARRY-371797 on functional capacity and cardiac function in patients with LMNA-related dilated cardiomyopathy. METHODS: Patients with LMNA-related dilated cardiomyopathy in New York Heart Association class II-IIIA, on background heart failure treatment, received ARRY-371797 100 or 400 mg twice daily for 48 weeks. The primary end point was change from baseline in the 6-minute walk test distance at 12 weeks. Secondary end points included changes over time in 6-minute walk test distance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration, left ventricular ejection fraction, and quality-of-life scores on the Kansas City Cardiomyopathy Questionnaire. Data from the 2 dose groups were combined. RESULTS: Twelve patients were enrolled; median (minimum, maximum) 6-minute walk test distance at baseline was 314 (246, 412) m. At week 12, the mean (80% CI) increase from baseline in 6-minute walk test distance was 69 (39, 100) m (median, 47 m). Median NT-proBNP concentration declined from 1409 pg/mL at baseline to 848 pg/mL at week 12. Mean left ventricular ejection fraction was stable at week 12. There was a trend toward improvement in Kansas City Cardiomyopathy Questionnaire Overall and Clinical Summary scores at week 12. No clinically significant drug-related safety concerns were identified. CONCLUSIONS: ARRY-371797 was well tolerated and resulted in potential increases in functional capacity and lower concentrations of cardiac biomarker NT-proBNP in patients with LMNA-related dilated cardiomyopathy. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02057341.

Diuretic dose trajectories in dilated cardiomyopathy: prognostic implications.

BACKGROUND: For patients with heart failure, prescription of loop diuretics (LD) and of higher doses are associated with an adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM). METHODS: Associations between outcomes and both furosemide-equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were classified as (i) dose↑ (FED increase by ≥ 50% or newly initiated); (ii) dose↓ (FED decrease by ≥ 50%); (iii) stable dose (change in FED by < 50%); and (iv) never-users. The primary outcome was all-cause-death/heart transplantation/ventricular-assist-device/heart failure hospitalization. The secondary outcome was all-cause-death/heart transplantation/ventricular-assist-device. RESULTS: Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04-1.22], p = 0.003). Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% were dose↓; 26% were stable dose and 14% were dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of the primary outcome (HR 2.42 [95% CI 1.19-4.93], p = 0.015), while dose↑ had the worst prognosis (HR 2.76 [95% CI 1.27-6.03], p = 0.011). Results were similar for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with an improved outcome (HR 0.43 [95% CI 0.28-0.65], p < 0.001). CONCLUSIONS: In patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never receive LD have an excellent prognosis. Among 1131 DCM patients 65% received loop diuretics at enrolment (upper left side). The bar chart on the upper right side shows the categorization in never-users/ dose↓/stable dose/ dose↑ over 24 months of follow-up. At the bottom is reported on the left side of each panel (observation period) the trajectory of LD dose in the four groups (left panel) and in patients who have their LD suspended vs those who continue LD (right panel) in the first two years. On the right side of each panel is shown the incidence of primary outcomes during the subsequent follow-up in the subgroups (outcome assessment).

Machine learning to predict left ventricular reverse remodeling by guideline-directed medical therapy by utilizing texture feature of extracellular volume fraction in patients with non-ischemic dilated cardiomyopathy.

Extracellular volume fraction (ECV) by cardiac magnetic resonance (CMR) allows for the non-invasive quantification of diffuse myocardial fibrosis. Texture analysis and machine learning are now gathering attention in the medical field to exploit the ability of diagnostic imaging for various diseases. This study aimed to investigate the predictive value of texture analysis of ECV and machine learning for predicting response to guideline-directed medical therapy (GDMT) for patients with non-ischemic dilated cardiomyopathy (NIDCM). A total of one-hundred and fourteen NIDCM patients [age: 63 ± 12 years, 91 (81%) males] were retrospectively analyzed. We performed texture analysis of ECV mapping of LV myocardium using dedicated software. We calculated nine histogram-based features (mean, standard deviation, maximum, minimum, etc.) and five gray-level co-occurrence matrices. Five machine learning techniques and the fivefold cross-validation method were used to develop prediction models for LVRR by GDMT based on 14 texture parameters on ECV mapping. We defined the LVRR as follows: LVEF increased ≥ 10% points and decreased LVEDV ≥ 10% on echocardiography after GDMT > 12 months. Fifty (44%) patients were classified as non-responders. The area under the receiver operating characteristics curve for predicting non-responder was 0.82 for eXtreme Gradient Boosting, 0.85 for support vector machine, 0.76 for multi-layer perception, 0.81 for Naïve Bayes, 0.77 for logistic regression, respectively. Mean ECV value was the most critical factor among texture features for differentiating NIDCM patients with LVRR and those without (0.28 ± 0.03 vs. 0.36 ± 0.06, p < 0.001). Machine learning analysis using the support vector machine may be helpful in detecting high-risk NIDCM patients resistant to GDMT. Mean ECV is the most crucial feature among texture features.

[Network Meta-analysis of 11 Chinese patent medicines in treatment of dilated cardiomyopathy].

Bayesian network Meta-analysis was performed to evaluate the efficacy and safety of different Chinese patent medicines in the treatment of dilated cardiomyopathy. The PubMed, EMbase, Cochrane Library, CNKI, Wanfang, and VIP were searched for the randomized controlled trial(RCT) from the inception to May 2023. The quality of the included RCT was evaluated by the Cochrane risk of bias assessment tool, and the data were analyzed by RStudio 3.6.3 calling the "gemtc" package. A total of 96 RCTs involving 8 452 patients, 11 Chinese patent medicines, and 8 outcome indicators were included. Network Meta-analysis is described as follows.(1)In terms of improving clinical total effective rate, except Yixinshu Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Xinshuai Mixture + conventional western medicine, the other Chinese patent medicines combined with conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(2)In terms of improving left ventricular ejection fraction(LVEF), except Yixinshu Capsules + conventional western medicine and Shensong Yangxin Capsules + conventional western medicine, other Chinese patent medicines combined with conventional western medicine outperformed conventional western medicine alone, and Shexiang Baoxin Pills + conventional western medicine had the best effect.(3)In terms of reducing left ventricular end-diastolic dimension(LVEDD), Getong Tongluo Capsules + conventional western medicine, Xinshuai Mixture + conventional western medicine, Huangqi Mixture + conventional western medicine, Tongxinluo Capsules + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were better than conventional western medicine alone, and Wenxin Granules + conventional western medicine had the best effect.(4)There was no significant difference in reducing left ventricular end-systolic diameter(LVESD) between Chinese patent medicines combined with conventional western medicine and conventional western medicine alone.(5)In terms of improving 6-minute walking trail(6MWT), Yangxinshi Tablets + conventional western medicine, Yixinshu Capsules + conventional western medicine, Shenqi Yiqi Dropping Pills + conventional western medicine, Wenxin Granules + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were superior to conventional western medicine alone, and Shenqi Yiqi Dropping Pills + conventional western medicine had the best effect.(6)In reducing brain natriuretic peptide(BNP), Xinshuai Mixture + conventional western medicine ourperformed conventional western medicine alone.(7)In reducing hypersensitive C-reactive protein(hs-CRP), Shenqi Yiqi Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine outperformed conventional western medicine alone, and Qili Qiangxin Capsules + conventional western medicine had the best effect.(8)In terms of safety, adverse reactions were reported in both groups. In conclusion, Chinese patent medicine combined with conventional western medicine were more effective in the treatment of dilated cardiomyopathy. The combinations relieve clinical symptoms and improve cardiac function indexes, and thus can be used according to the patients' conditions in clinical practice. However, limited by the quality and sample size of the included studies, the conclusion remains to be verified by multi-center, large-sample, and high-quality RCT in the future.

Hydroxychloroquine Mitigates Dilated Cardiomyopathy Phenotype in Transgenic D94A Mice.

In this study, we aimed to investigate whether short-term and low-dose treatment with hydroxychloroquine (HCQ), an antimalarial drug, can modulate heart function in a preclinical model of dilated cardiomyopathy (DCM) expressing the D94A mutation in cardiac myosin regulatory light chain (RLC) compared with healthy non-transgenic (NTg) littermates. Increased interest in HCQ came with the COVID-19 pandemic, but the risk of cardiotoxic side effects of HCQ raised concerns, especially in patients with an underlying heart condition, e.g., cardiomyopathy. Effects of HCQ treatment vs. placebo (H2O), administered in Tg-D94A vs. NTg mice over one month, were studied by echocardiography and muscle contractile mechanics. Global longitudinal strain analysis showed the HCQ-mediated improvement in heart performance in DCM mice. At the molecular level, HCQ promoted the switch from myosin's super-relaxed (SRX) to disordered relaxed (DRX) state in DCM-D94A hearts. This result indicated more myosin cross-bridges exiting a hypocontractile SRX-OFF state and assuming the DRX-ON state, thus potentially enhancing myosin motor function in DCM mice. This bottom-up investigation of the pharmacological use of HCQ at the level of myosin molecules, muscle fibers, and whole hearts provides novel insights into mechanisms by which HCQ therapy mitigates some abnormal phenotypes in DCM-D94A mice and causes no harm in healthy NTg hearts.

The effect of dilated cardiomyopathy with moyamoya disease in a 31-year-old Chinese man: A case report.

BACKGROUND: Dilated cardiomyopathy (DCM) is a clinically common and refractory disease; however, few cases of dilated cardiomyopathy have been reported in patients with moyamoya diseases treated by combining traditional Chinese Medicine (TCM) and Western medicine, which has a higher risk of rehabilitation. CASE SUMMARY: A 31-year-old man was admitted due to paroxysmal chest tightness and shortness of breath. He denied a history of DCM, hypertension, diabetes, pericarditis, smoking, and alcohol consumption. On admission, his transesophageal echocardiography (Fig. 1A) showed the larger heart with poor myocardial systolic function (left ventricular end diastolic diameter [LVEDd] 60 mm, left ventricular ejection fraction [LVEF] 38% [Teich]). On day 14 of admission, heart-related indicators were better than before. CONCLUSION: The present case is the first report demonstrating appearance the dilated cardiomyopathy (DCM) and moyamoya disease simultaneously in a 31-year-old Chinese man, aimed to report the treatment of such patients using a combination of TCM and Western medicine and analyzing the necessity and advantages of using this treatment for patients suffering from DCM and moyamoya disease, so as to improve the level of clinical diagnosis and treatment of such diseases.