Non-obstructive hypertrophic cardiomyopathy (nHCM) is a condition that has significant therapeutic challenges due to its complicated pathophysiology. Beta-blockers (BB) and calcium channel blockers (CCB) are the existing treatment modalities that offer limited symptom relief and fail to address underlying metabolic deficits. This review evaluates emerging targeted therapies, focusing on ninerafaxstat, a cardiac metabolic modulator that inhibits 3-ketoacyl-CoA thiolase (3-KAT) to shift myocardial substrate utilization from fatty acids to glucose, thereby improving energy efficiency. Clinical trials of novel agents, including myosin inhibitors (aficamten, mavacamten) and metabolic modulators, highlight ninerafaxstat's unique potential. The Phase 2 IMPROVE-HCM trial demonstrated improved ventilatory efficiency (VE/VCO2 slope: -2.1, P=0.005), reduced left atrial remodeling (-0.9 mm, P=0.01), and enhanced quality of life in severe subgroups, with a favorable safety profile. Unlike myosin inhibitors, which reduce hypercontractility but not energy deficits, ninerafaxstat directly resolves metabolic dysfunction, synergizing with sarcomere-targeted therapies for dual-pathway efficacy. While myosin inhibitors (e.g., REDWOOD-HCM, MAVERICK-HCM) show robust biomarker improvements, ninerafaxstat addresses the core energy mismatch driving nHCM progression. Innovative gene therapies (MyPEAK-1) and exercise programs broaden the range of available treatments. Ninerafaxstat represents a paradigm shift toward precision medicine in nHCM, offering a metabolic foundation for combination strategies. Future Phase 3 trials must validate long-term benefits on functional capacity, metabolic markers, arrhythmia risk, and survival, positioning ninerafaxstat as a cornerstone therapy for restoring cardiac energetics in nHCM.

Protein kinase C (PKC) isoforms are crucial in hypertension-associated vascular dysfunction. Our previous study suggested that upregulated PKCβ2 contributed to aorta hypercontraction in spontaneously hypertensive rats (SHR). However, its role in resistance arteries remains unclear. Considering the implications of sphingosine 1-phosphate (S1P) and its receptors (S1PRs) in hypertensive vascular dysfunction, we investigated whether PKCβ2 is regulated by S1P in SHR mesenteric arteries and elucidated its underlying mechanisms. Functional studies were performed on endothelium-denuded mesenteric arteries isolated from SHR and Wistar-Kyoto (WKY) rats. Expression of PKCβ2, S1P2, S1P3, and phosphorylation levels of PKCβ2 and key proteins in calcium sensitization pathway were assessed by Western blotting using mesenteric arteries and mesenteric arterial smooth muscle cells (MASMCs). PKCβ2 expression was significantly elevated in SHR. LY333531, a PKCβ inhibitor, attenuated contraction induced by norepinephrine and S1P in SHR. S1P significantly increased PKCβ2 phosphorylation in SHR, an effect suppressed by sphingosine kinase 1 inhibitor PF-543. Inhibition or silencing of PKCβ2 significantly suppressed S1P-induced calcium sensitization. The expression levels of S1P2 and S1P3 were markedly higher in SHR, and the inhibitory effect of LY333531 on S1P-induced contraction was not altered by JTE-013 (an S1P2 antagonist) or TY-52156 (an S1P3 antagonist). Furthermore, inhibition or silencing of S1P2 or S1P3 suppressed the activation of PKCβ2 and downstream calcium sensitization pathway. These findings demonstrate that S1P activates PKCβ2 via S1P2 and S1P3, enhancing calcium sensitization pathway and promoting hypercontraction in SHR. Thus, the S1P/PKCβ2 pathway is a potential therapeutic target for hypertensive vascular dysfunction.

This study aimed to evaluate the efficacy of angiotensin-converting enzyme inhibitors (ACEi) in preventing anthracycline-induced cardiotoxicity in patients undergoing anthracycline-based chemotherapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing ACEi with standard treatment/placebo for cardiotoxicity prevention in patients undergoing anthracycline-based chemotherapy. We pooled outcomes of echocardiographic and cardiac biomarker changes. A random-effects model was used for all outcomes. We included 7 RCTs with 686 patients, of whom 346 (50%) received prophylaxis with ACEi. The most common malignancy was breast cancer, and the follow-up ranged from 6 to 31 months. Prophylactic use of ACEi was associated with a significantly smaller reduction in left ventricular ejection fraction (LVEF) compared with the control group {mean difference (MD) -5% [95% confidence interval (CI) -8% to -2%]; P < 0.010}. Subgroup analysis limited to studies excluding trastuzumab from the chemotherapy regimens showed no significant difference [MD -7% (95% CI -16% to 2%); P = 0.110]. By contrast, in studies including trastuzumab-containing regimens, ACEi demonstrated a statistically significant effect in limiting LVEF reduction [MD -3%, (95% CI -4 to -1); P < 0.010]. Diastolic function (E/A ratio) changes [MD 0.0 (95% CI -0.1 to 0.09); I 2 = 36.3%] and relative risk of increased troponin I at follow-up [Risk-Ratios 0.58 (95% CI 0.17-1.94); I 2 = 69.6%] were not statistically significant. Prophylactic ACEi administration in patients undergoing anthracycline-based chemotherapy was associated with a smaller decline in LVEF. This protective role may be more relevant in patients also receiving trastuzumab. More powered and longer follow-up studies are needed to confirm these findings.

Coronary heart disease (CHD) remains a leading cause of cardiovascular morbidity and mortality worldwide, posing a global health threat. In recent years, angiotensin-like proteins (ANGPTLs) have emerged as a research focus in CHD due to their critical role in regulating lipid metabolism and inflammation. ANGPTLs are a class of secreted glycoproteins that primarily regulate lipid metabolism by influencing lipoprotein lipase activity. Dysfunction of these proteins leads to dyslipidemia, thereby promoting the formation of atherosclerotic plaques. Additionally, ANGPTLs act as pro-inflammatory factors, accelerating the development of endotheliitis. Current ANGPTL-targeted therapeutic strategies (monoclonal antibodies, small interfering RNA) have advanced to clinical trial stages, demonstrating favorable safety, tolerability, and lipid-lowering effects in humans. These approaches hold promise as novel preventive and therapeutic measures for CHD. This paper aims to elucidate the multifaceted role of ANGPTLs in CHD, summarize existing drug research, and outline future research directions, emphasizing the broad prospects of ANGPTL-targeted therapies in CHD prevention and treatment.

Human arterial blood pressure follows a circadian rhythm, where pressure is highest during the day and lowest during the night. Patients with hypertension can have either a preserved rhythm or a dampened rhythm with a lower day-to-night difference, called "dippers" and "nondippers," respectively. Spironolactone, eplerenone, and the newer finerenone are mineralocorticoid receptor antagonists (MRAs) used for patients with resistant hypertension. In this study, we describe the 24h diurnal cycle in blood pressure in mice with and without hypertension to test whether high blood pressure induced a nondipping phenotype. Moreover, we tested whether the 3 MRAs affected the 24h cycles in blood pressure in the mice. Radiotelemetry devices were used to monitor blood pressure continuously in freely roaming mice (n = 19). Hypertension was induced by l -nitroarginine methyl ester ( l -NAME, 1 g/L) dissolved in the drinking water. A dipping phenotype was acknowledged if the nocturnal reduction in blood pressure was >10%. The 3 MRAs were administered orally once daily. Significant 24h rhythms were identified in blood pressure and 89% of the mice had a dipping phenotype at baseline. Only 42% of the hypertensive mice were dippers ( P > 0.05 vs. baseline). The MRAs at the doses tested did not change the 24h rhythm in blood pressure, and they did not restore a dipping phenotype in the nondipping hypertensive mice. Thus, l -NAME causes hypertension in mice and induces a "nondipper" phenotype in most of the mice. Spironolactone, eplerenone, or finerenone at the selected doses do not change arterial blood pressure in hypertensive mice.

Few surveys have focused on a patient's journey or healthcare professionals' (HCPs') perspectives in treating inflammation in atherosclerotic cardiovascular disease (ASCVD). Patients with ASCVD (n=200) and HCPs (n=204) completed separate 30-minute, online questionnaires between 6/24 and 8/24. HCPs included cardiologists (83%) and cardiology NPs or PAs (17%). Patients that completed the survey, however, were not linked to the HCP's that participated. Among patients with ASCVD, HCPs reported initiation rates of statin and antiplatelet therapy at 78% and 65%, respectively. Only a limited number of patients (18%) believed their treatment was working extremely well, with 82% reporting persistent symptoms, including chest pain (28%), issues walking (28%), or issues breathing and/or cough (26%). Most HCPs (87%) believed that residual cardiovascular risk remained after modifying traditional ASCVD risk factors. Two-thirds (66%) of HCPs agreed that inflammation is an important component in ASCVD, not sufficiently addressed by current treatments and only 58% reported being mostly to extremely satisfied with current ASCVD treatments. Approximately 29% of cardiologists reported that they measured high-sensitivity C-reactive protein (hsCRP) often or always, and of those, 79% did so due to the presence or suspicion of an inflammatory comorbidity. Uncertainty exists about the evaluation and treatment of inflammation in patients with ASCVD. Ongoing studies evaluating anti-inflammatory therapies will help to inform future hsCRP testing in the ASCVD population.

The impact of blood pressure (BP) reduction induced by levosimendan infusion on in-hospital mortality in patients with acute heart failure (AHF) and systolic ventricular dysfunction still needs to be clarified. We conducted a retrospective cohort study involving 161 patients hospitalized for AHF and treated with a 24-hour infusion of levosimendan between 2017 and 2024, following a standard protocol. During hospitalization, biometric, clinical, laboratory, and echocardiographic parameters were assessed. The results revealed that the difference in systolic and mean BP before and after levosimendan infusion (delta-SBP and delta-MAP) were significantly associated with higher in-hospital mortality (delta-SBP in survivors: 10.1±19.1 mmHg vs. in non-survivors: 21.4±23.6 mmHg, p=0.023; delta-MAP in survivors: 8.8±15.8 mmHg vs. in non-survivors: 17.8±23.3 mmHg, p=0.034), regardless of baseline BP values and despite the fact that the majority of patients had absolute values of SBP after levosimendan infusion >90 mmHg. Multivariable analysis confirmed that a larger reduction in SBP was an independent predictor of in-hospital mortality (OR: 1.053, 95% CI: 1.015-1.092, p=0.006). Absolute values of SBP after levosimendan infusion (post-SBP) were also independently associated with mortality (OR: 0.942, 95% CI: 0.896-0.990, p=0.019). However, when the analysis was repeated in a subgroup of subjects with SBP after infusion >90 mmHg, only delta-SBP remained independently associated with mortality (OR 1.051, 95% CI 1.009-1.095, p=0.017). In patients with AHF treated with levosimendan, larger reductions in SBP after therapy are independently associated with in-hospital mortality. Monitoring SBP changes after levosimendan infusion may improve risk stratification and guide clinical decisions.

Somatostatin and analogues may reduce chest tube (CT) output in chylothorax caused by post-coronary artery bypass grafting (CABG). However, data is limited to case reports and series. This scoping review aimed to describe the efficacy and safety of somatostatin/analogue use in post-CABG chylothorax. We retrieved from PubMed, Embase, and OVID all studies and case reports describing somatostatin/analogue use in adult patients post-CABG for resolution of chylothorax. The primary outcome was time from somatostatin/analogue initiation to daily CT output <100 mL/day. Chest tube duration, need to repeat invasive intervention, and safety events associated with somatostatin/analogues were also analyzed. Somatostatin/analogues were associated with reductions in CT output, but one-third of patients still required pleurodesis or surgical intervention. No safety events were identified. Patients with lower daily CT outputs at the time of somatostatin/analogue initiation were more likely to avoid repeat intervention than those with higher outputs. In conclusion, somatostatin/analogues appear safe and possibly effective in management of post-CABG chylothorax. Future studies should investigate which patients are most likely to benefit from this therapy.