Sacubitril/valsartan attenuates atrial conduction disturbance and electrophysiological heterogeneity with ameliorating fibrosis in mice.

Background: Sacubitril/valsartan (SacVal) has been shown to improve the prognosis of heart failure; however, whether SacVal reduces the occurrence of atrial fibrillation (AF) in heart failure has not yet been elucidated. In this study, we aimed to determine whether SacVal is effective in reducing the occurrence of AF in heart failure and identify the underlying mechanism of its electrophysiological effect in mice. Methods: Adult male mice underwent transverse aortic constriction, followed by SacVal, valsartan, or vehicle treatment for two weeks. Electrophysiological study (EPS) and optical mapping were performed to assess the susceptibility to AF and the atrial conduction properties, and fibrosis was investigated using heart tissue and isolated cardiac fibroblasts (CFs). Results: EPS analysis revealed that AF was significantly less inducible in SacVal-treated mice than in vehicle-treated mice. Optical mapping of the atrium showed that SacVal-treated and valsartan-treated mice restored the prolonged action potential duration (APD); however, only SacVal-treated mice showed the restoration of decreased conduction velocity (CV) compared to vehicle-treated mice. In addition, the electrophysiological distribution analysis demonstrated that heterogeneous electrophysiological properties were rate-dependent and increased heterogeneity was closely related to the susceptibility to AF. SacVal attenuated the increased heterogeneity of CV at short pacing cycle length in atria, whereas Val could not. Histological and molecular evaluation showed that SacVal exerted the anti-fibrotic effect on the atria. An in vitro study of CFs treated with natriuretic peptides and LBQ657, the metabolite and active form of sacubitril, revealed that C-type natriuretic peptide (CNP) combined with LBQ657 had an additional anti-fibrotic effect on CFs. Conclusions: Our results demonstrated that SacVal can improve the conduction disturbance and heterogeneity through the attenuation of fibrosis in murine atria and reduce the susceptibility of AF in heart failure with pressure overload, which might be attributed to the enhanced function of CNP.

Impact of red blood cell distribution width on non-cardiac mortality in patients with acute decompensated heart failure with preserved ejection fraction.

BACKGROUND: The prognostic impact of red blood cell distribution width (RDW) on adverse outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is unclear. We investigated the association between RDW values at admission and long-term prognosis in patients with acute decompensated HFpEF. METHODS: The present study enrolled 278 consecutive patients with acute decompensated HFpEF, whose RDW levels were measured at admission. We divided enrolled patients into 2 groups according to RDW value and investigated the association between RDW and patients' mortality. RESULTS: A Kaplan-Meier analysis demonstrated that patients with higher RDW levels had significantly higher all-cause and non-cardiac mortality, but not cardiac-based mortality, than did patients with lower RDW levels. A multivariate Cox regression analysis revealed that RDW levels were independently correlated with all-cause and non-cardiac mortality after adjusting for other risk factors, including age, brain natriuretic peptide, hemoglobin, and Charlson comorbidity index score. In a receiver-operating curve analysis, the cut-off value to maximize the prognostic impact of RDW on mortality was 15.2%. The evaluation of RDW and other prognostic factors improved their predictive value for both all-cause and non-cardiac mortality. CONCLUSIONS: The current study demonstrated that RDW levels at admission independently predict poor outcomes because of non-cardiac events in patients with acute decompensated HFpEF. Evaluation of RDW could provide useful information for the long-term prognosis of HFpEF.

Early Spontaneous Remission of Intramyocardial Dissecting Hematoma.

Intramyocardial dissecting hematoma is a rare but potentially fatal complication of myocardial infarction. The decision to adopt a surgical or conservative strategy may depend on the clinical and hemodynamic stability of patients. Regardless, the precise and temporal assessment of the structure of hematoma is imperative. We herein report the first case of a patient with early spontaneous remission of intramyocardial dissecting hematoma successfully managed by a conservative approach with multimodality imaging.

Lipoprotein(a) levels predict adverse vascular events after acute myocardial infarction.

Lipoprotein(a) [Lp(a)], which is genetically determined, has been reported as an independent risk factor for atherosclerotic vascular disease. However, the prognostic value of Lp(a) for secondary vascular events in patients after coronary artery disease has not been fully elucidated. This 3-year observational study included a total of 176 patients with ST-elevated myocardial infarction (STEMI), whose Lp(a) levels were measured within 24 h after primary percutaneous coronary intervention. We divided enrolled patients into two groups according to Lp(a) level and investigated the association between Lp(a) and the incidence of major adverse cardiac and cerebrovascular events (MACCE). A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of MACCE than those with lower Lp(a) levels (log-rank P = 0.034). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the occurrence of MACCE after adjusting for other classical risk factors of atherosclerotic vascular diseases (hazard ratio 1.030, 95 % confidence interval: 1.011-1.048, P = 0.002). In receiver-operating curve analysis, the cutoff value to maximize the predictive power of Lp(a) was 19.0 mg/dl (area under the curve = 0.674, sensitivity 69.2 %, specificity 62.0 %). Evaluation of Lp(a) in addition to the established coronary risk factors improved their predictive value for the occurrence of MACCE. In conclusion, Lp(a) levels at admission independently predict secondary vascular events in patients with STEMI. Lp(a) might provide useful information for the development of secondary prevention strategies in patients with myocardial infarction.

Clinical benefit of tolvaptan in patients with acute decompensated heart failure and chronic kidney disease.

Tolvaptan, a vasopressin type 2 receptor antagonist, has an aquaretic effect without affecting renal function. The effects of long-term tolvaptan administration in heart failure patients with renal dysfunction have not been clarified. Here, we assessed the clinical benefit of tolvaptan during a 6-month follow-up in acute decompensated heart failure (ADHF) patients with severe chronic kidney disease (CKD; estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m(2)). We compared 33 patients with ADHF and severe CKD who were administered tolvaptan in addition to loop diuretics (TLV group), with 36 patients with ADHF and severe CKD who were administered high-dose loop diuretics (≥40 mg) alone (LD group). Alterations in serum creatinine and eGFR levels from the time of hospital discharge to 6-month follow-up were significantly different between the groups, with those in the TLV group being more favorable. Furthermore, Kaplan-Meier analysis revealed that rehospitalization for heart failure (HF) was significantly lower in the TLV group compared with the LD group. In ADHF patients with severe CKD, tolvaptan use for 6 months reduced worsening of renal function and rehospitalization rates for HF when compared with conventional diuretic therapy. In conclusion, tolvaptan could be a safe and effective agent for long-term management of HF and CKD.