Native T1 high region and left ventricular ejection fraction recovery in patients with dilated cardiomyopathy.

Native T1 mapping is used to assess myocardial tissue characteristics without gadolinium contrast agents. The focal T1 high-intensity region can indicate myocardial alterations. This study aimed to identify the association between the native T1 mapping including the native T1 high region and left ventricular ejection fraction (LVEF) recovery in patients with dilated cardiomyopathy (DCM). Patients with newly diagnosed DCM (LVEF of < 45%) who underwent cardiac magnetic resonance imaging with native T1 mapping were included in the analysis. Native T1 high region was defined as a signal intensity of > 5 SD in the remote myocardium. Recovered EF was defined as a follow-up LVEF of ≥ 45% and an LVEF increase of ≥ 10% after 2 years from baseline. Seventy-one patients met the inclusion criteria for this study. Forty-four patients (61.9%) achieved recovered EF. Logistic regression analysis showed that the native T1 value (OR: 0.98; 95% CI: 0.96-0.99; P = 0.014) and the native T1 high region (OR: 0.17; 95% CI: 0.05-0.55; P = 0.002), but not late gadolinium enhancement, were independent predictors of recovered EF. Compared with native T1 value alone, combined native T1 high region and native T1 value improved the area under the curve from 0.703 to 0.788 for predicting recovered EF. Myocardial damage, which was quantified using native T1 mapping and the native T1 high region were independently associated with recovered EF in patients with newly diagnosed DCM.

Direct observation of Mn distribution/speciation within and surrounding a basidiomycete fungus in the production of Mn-oxides important in toxic element containment.

Biogenic manganese (Mn) oxides occur ubiquitously in the environment including the uranium (U) mill tailings at the Ningyo-toge U mine in Okayama, Japan, being important in the sequestration of radioactive radium. To understand the nanoscale processes in Mn oxides formation at the U mill tailings site, Mn2+ absorption by a basidiomycete fungus, Coprinopsis urticicola, isolated from Ningyo-toge mine water samples, was investigated in the laboratory under controlled conditions utilizing electron microscopy, synchrotron-based X-ray analysis, and fluorescence microscopy with a molecular pH probe. The fungus' growth was first investigated in an agar-solidified medium supplemented with 1.0 mmol/L Mn2+, and Cu2+ (0-200 µM), Zn2+ (0-200 µM), or diphenyleneiodonium (DPI) chloride (0-100 µM) at 25 °C. The results revealed that Zn2+ has no significant effects on Mn oxide formation, whereas Cu2+ and DPI significantly inhibit both fungal growth and Mn oxidation, indicating superoxide-mediated Mn oxidation. Indeed, nitroblue tetrazolium and diaminobenzidine assays on the growing fungus revealed the production of superoxide and peroxide. During the interaction of Mn2+ with the fungus in solution medium at the initial pH of 5.67, a small fraction of Mn2+ infiltrated the fungal hyphae within 8 h, forming a few tens of nm-sized concentrates of soluble Mn2+ in the intracellular pH of ∼6.5. After 1 day of incubation, Mn oxides began to precipitate on the hyphae, which were characterized as fibrous nanocrystals with a hexagonal birnessite-structure, these forming spherical aggregates with a diameter of ∼1.5 µm. These nanoscale processes associated with the fungal species derived from the Ningyo-toge mine area provide additional insights into the existing mechanisms of Mn oxidation by filamentous fungi at other U mill tailings sites under circumneutral pH conditions. Such processes add to the class of reactions important to the sequestration of toxic elements.

Inhaled nitric oxide for ECPELLA management in fulminant myocarditis complicated with severe right ventricular dysfunction: A case report.

Combination therapy with venoarterial extracorporeal membrane oxygenation (VA-ECMO) and Impella (ECPELLA) has been known to be a favorable strategy of mechanical circulation support for patients with fatal cardiogenic shock. However, the practical strategy for weaning ECPELLA in patients with right ventricular (RV) dysfunction remains unclear. We describe a case of a 63-year-old male with fulminant myocarditis presenting with cardiogenic shock who required ECPELLA to improve hemodynamics. Because of persistent severe RV dysfunction despite the introduction of intravenous dobutamine and milrinone, VA-ECMO could not be weaned. Inhaled nitric oxide (iNO) was introduced at 20 ppm to reduce RV afterload, resulting in increased cardiac output (from 1.6 to 5.5 L/min) and ameliorated RV performance (the pulmonary artery pulsatility index was from 0.47 to 1.11). Subsequently, VA-ECMO could be weaned. iNO, a selective pulmonary vasodilator, reduces pulmonary vascular resistance, resulting in reduced RV afterload. This is the first case of iNO usage for the management of cardiogenic shock supported by ECPELLA. iNO could be a favorable strategy in ECPELLA patients with refractory RV dysfunction for weaning VA-ECMO through bridging to recovery. Learning objective: The practical strategy for weaning venoarterial extracorporeal membrane oxygenation and Impella (ECPELLA) in patients with concomitant right ventricular dysfunction remains unclear. Inhaled nitric oxygen is a novel weaning strategy for patients with biventricular dysfunction supported by ECPELLA. If the response of inhaled nitric oxygen was insufficient under ECPELLA support, implantable ventricular assist devices or transplantation should be considered.

Hemodynamic assessment and risk classification for successful weaning of Impella in patients with cardiogenic shock.

BACKGROUND: Clinical predictors for successful weaning of patients from Impella heart pump have not been clarified. We aimed to elucidate the relationship between pulmonary artery catheter (PAC) parameters at the time of Impella weaning and subsequent outcomes. METHODS: We enrolled consecutive patients who had received Impella for cardiogenic shock. PAC data were collected immediately before Impella weaning. Patients were classified as non-survivors if they died or required any mechanical circulatory support reintroduction within 30 days of weaning. RESULTS: Of 81 patients enrolled, 61 underwent Impella weaning. Of these, 16 were non-survivors. Predictive indicators of non-survival were high pulmonary artery wedge pressure (PAWP; hazard ratio [HR] per 5 mm Hg 1.97, 95% CI 1.35-2.80; p < 0.001), high mean pulmonary artery pressure (MPAP; HR per 5 mm Hg 1.90, 1.38-2.58; p < 0.001), and low cardiac power output (CPO; HR per 0.1 Watts 0.71, 0.52-0.92; p = 0.006). Cutoff values of PAWP 20 mm Hg, MPAP 22 mm Hg, and CPO 0.59 Watts showed strong associations with 30-day non-survival risk (low risk 8% in patients with low PAWP and high CPO or 4% in patients with low MPAP and high CPO; high risk 100% in patients with high PAWP and low CPO or 82% in patients with high MPAP and low CPO). CONCLUSIONS: PAWP or MPAP higher than the cutoff with CPO below the cutoff at Impella weaning were associated with worse outcomes. We proposed a risk classification model for successful Impella weaning using PAC.

Re-worsening left ventricular ejection fraction after response to cardiac resynchronization therapy.

BACKGROUND: Although cardiac resynchronization therapy (CRT) provided functional and clinical improvement in patients with heart failure (HF) and electrical intraventricular conduction disturbances, some patients had re-worsening left ventricular (LV) function after a favorable CRT response. We analyzed the clinical variables and cardiac outcomes associated with this re-worsening LV function after CRT. METHODS: In this study, 71 patients with CRT response who received CRT between 2006 and 2017 were included. CRT response was defined as a "≥ 10% improvement in LV ejection fraction (LVEF) on follow-up." Patients were classified into two groups: (i) persistent: (n = 48, 68%), defined as those with a CRT response and (ii) re-worsening: (n = 23, 32%), consisting of those who fell out of the definition of a CRT response after an initial CRT response. RESULTS: Half of the patients in the re-worsening group failed to maintain a CRT response from two years upwards. A longer duration from HF diagnosis to CRT implantation, nonspecific intraventricular conduction delay (NIVCD) on electrocardiogram at CRT implantation, and a lower increased LVEF at initial CRT response were independent predictors for the re-worsening group. Patients in the re-worsening group had a higher incidence rate for HF hospitalization and cardiac deaths, compared with those in the persistent group. CONCLUSION: One-third of CRT responders experienced re-worsening LVEF, which was associated with poor outcomes. CRT responders with NIVCD, longer HF duration, and a lower increased LVEF at initial CRT response should be monitored with caution.

Clinical valuables related to resolution of complete or advanced atrioventricular block after steroid therapy in patients with cardiac sarcoidosis.

BACKGROUND: Prediction of atrioventricular block (AVB) resolution after steroid therapy in patients with cardiac sarcoidosis (CS) is difficult. METHODS: We identified 24 patients with CS and complete or advanced AVB receiving steroid therapy. AVB resolution was assessed by reviewing surface electrocardiogram and the percentage of ventricular pacing required on subsequent device interrogation reports. RESULTS: AVB resolution was noted in eight (33%) patients 1 year after receiving steroid therapy. Univariate Cox regression analysis demonstrated that left ventricular ejection fraction (LVEF) (hazard ratio [HR] 1.07, 95% confidence interval [CI] 1.01-1.14, P = .016), interval from recognized AVB to start of steroid therapy (HR 0.98, 95% CI 0.95-0.99, P < .001), and lysozyme (HR 1.51, 95% CI 1.12-2.19, P = .013) were significantly associated with resolution of AVB. Combination of area under the curve (AUC) of each variable that was significantly related to resolution of AVB (AUC, 0.969; 95% CI 0.921-1.000, P < .001) was tended to be higher compared with each variable alone. CONCLUSIONS: A shorter interval from recognition of AVB to start of steroid therapy, higher LVEF, and higher lysozyme levels were significantly associated with resolution of AVB after steroid therapy in patients with CS. The combination of each variable could be able to distinguish patients with resolution of AVB from those without.

Association between intestinal oedema and oral loop diuretic resistance in hospitalized patients with acute heart failure.

AIMS: Intestinal oedema is one of the manifestations associated with right-sided heart failure (HF), which is known to be associated with poorer patient outcomes. We attempted to reveal the association between intestinal oedema and diuretic resistance in hospitalized patients with acute HF. METHODS AND RESULTS: Among 213 hospitalized patients with acute HF, abdominal ultrasonography was performed under clinically stable conditions after initial HF treatments. The association among abdominal ultrasonographic parameters, maintenance doses of loop diuretics, and responsiveness to initial loop diuretic treatment was evaluated. Higher mean colon wall thickness (CWT) independently correlated with a higher dose of loop diuretics at enrolment (adjusted ß = 0.198, P = 0.0004). Increased mean CWT also correlated with poor response to oral loop diuretics as an initial treatment, whereas it did not correlate with the response to intravenous loop diuretics. Discrimination of non-responders to initial oral loop diuretics resulted in a sensitivity of 0.772 and a specificity of 0.733 using a mean CWT cut-off value of ≥3 mm. CONCLUSIONS: In hospitalized patients with acute HF, a strong correlation was identified among the severity of intestinal oedema, required quantities as maintenance loop diuretic doses, and poor responsiveness to oral loop diuretics at admission.

Clinical significance of ischemia-like electrocardiographic finding during heart failure treatment on left ventricular recovery in patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: Patients with non-ischemic dilated cardiomyopathy (DCM) often show ischemia-like electrocardiographic findings. We aimed to elucidate the clinical impact of ischemia-like electrocardiographic findings in DCM, focusing on left ventricular reverse remodeling (LVRR). METHODS: We evaluated 195 patients hospitalized with heart failure (HF) and diagnosed with DCM. All patients underwent twelve-lead electrocardiography (ECG) and echocardiography during hospitalization and at the 2-year follow-up. RESULTS: During hospitalization, 152 (78%) patients experienced ischemia-like ECG findings (Minnesota codes I3, IV1-3, V1-3, or VII1); 43 patients (22%, non-ischemia-like group) did not experience these findings. Ischemia-like ECG findings were normalized during hospitalization in 64 patients (33%, transient-ischemia-like group) but were unchanged in 88 patients (45%, persistent-ischemia-like group). The highest rates of LVRR, defined as an increase in LV ejection fraction from ≥10% to a final value of ≥35%, along with decreased LV end-diastolic dimension of ≥10% during 2 years of follow-up, were shown in the transient-ischemia-like group (transient-ischemia-like group, 91%; persistent-ischemia-like group, 40%; non-ischemia-like-group, 51%; p < 0.001). The transient-ischemia-like group had lowest composite event rates, including readmission for HF, the detection of major ventricular arrhythmia, and sudden cardiac death. CONCLUSIONS: Normalization of ischemia-like ECG findings during the first HF treatments was associated with a higher occurrence of mid-term LVRR and favorable long-term outcome in patients with DCM.

Glucose-dependent diuresis in relation to improvements in renal-tubular markers of sodium-glucose cotransporter-2 inhibitors in hospitalized heart failure patients with diabetes.

Clinical parameters with correlation to diuretic effects after initiation of sodium-glucose cotransporter-2 (SGLT2) inhibitors are unclear. We aimed to identify the factors associated with the diuretic effect observed following the initiation of SGLT2 inhibitors in patients with diabetes having an acute heart failure (HF). Fifty-six patients included were hospitalized for acute HF with diabetes and started on SGLT2 inhibitors. Changes in urine volume (ΔUV) and blood/urine laboratory parameters before and during the first 4 days of therapy were evaluated. Data were prospectively obtained under clinically stable conditions after initial HF treatment. UV increased following the initiation of SGLT2 inhibitors [UV at baseline (BL): 1383 ± 479 mL/day; ΔUV over 4 days: + 189 ± 358 mL/day]. Multivariate analysis revealed no association between BL-hemoglobin A1c or BL-estimated glomerular filtration rate and ΔUV. Conversely, higher BL-fasting plasma glucose (FPG) and higher BL-urine N-acetyl-ß-D-glucosaminidase (NAG) were associated with a higher ΔUV. ΔUV was inversely associated with ΔFPG and ΔNAG, and positively associated with Δurinary sodium excretion. Elevated FPG and NAG both improved over 4 days of treatment. In conclusion, the diuretic effect of SGLT2 inhibitors was glycemia-dependent, and was associated with a reduction in elevated renal-tubular markers in hospitalized HF complicated with diabetes.

Late gadolinium enhancement for re-worsening left ventricular ejection fraction in patients with dilated cardiomyopathy.

AIMS: This study aimed to evaluate the clinical parameters including late gadolinium enhancement (LGE) of cardiovascular magnetic resonance to predict re-worsening of left ventricular ejection fraction (LVEF) in patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We included 138 patients with recent-onset DCM who had an LVEF <45% and underwent LGE of cardiovascular magnetic resonance imaging at diagnosis and echocardiography at the yearly follow-up [median 6 (4-8.3) years]. Initial LVEF recovery was defined as LVEF increase >10% from baseline, resulting in LVEF ≧45% after treatment. The patients were divided into three groups: (i) improved (n = 83, 60%), defined as those with sustained LVEF ≧45%; (ii) re-worsening (n = 39, 28%), those with >5% decrease and LVEF <45% after the initial LVEF recovery; and (iii) not-improved (n = 16, 12%), those without initial LVEF recovery. The primary endpoint was a composite of hospitalization for heart failure or sudden cardiac death. In baseline, LGE was observed in 70 patients. The LGE area was significantly larger in the re-worsening and not-improved groups than that in the improved group (P < 0.001). Loess curves of long-term LVEF trajectories showed that LVEF in the re-worsening group increased in the first 2 years and slowly declined thereafter. Multivariate logistic regression analysis demonstrated that LGE area [odds ratio (OR) 1.09, 95% confidence interval (CI) 1.03-1.16, P = 0.004], B-type natriuretic peptide (OR 1.49, 95% CI 1.05-2.21, P = 0.030) level at the initial recovery, and LVEF (OR 0.91, 95% CI 0.86-0.97, P = 0.004) at the initial LVEF recovery were independent predictors of re-worsening of LVEF. During a median follow-up of 2273 (interquartile range: 1634-3191) days, the primary endpoint was observed in 31 (22%) patients. Univariate Cox proportional hazards analysis demonstrated that the risk of experiencing the primary event in the re-worsening group was significantly higher (hazard ratio: 4.30, 95% CI 1.63-11.31, P = 0.003) than that in the improved group and was lower than that in the not-improved group (hazard ratio: 0.33, 95% CI 0.15-0.72, P = 0.006). CONCLUSIONS: Re-worsening of LVEF was observed in 28% of patients with recent-onset DCM who showed an initial improvement in LVEF. High LGE burden, higher B-type natriuretic peptide level, and lower LVEF at the initial LVEF recovery were independent predictors of re-worsening of LVEF in patients with DCM. Careful observation is recommended for patients with a high risk for re-worsening of LVEF, even in those with an initial LVEF recovery.

Clinical significance of left atrial geometry in dilated cardiomyopathy patients: A cardiovascular magnetic resonance study.

BACKGROUND: Clinical significance of left atrial (LA) function and geometry in patients with dilated cardiomyopathy (DCM) remains uncertain. HYPOTHESIS: LA geometric parameters assessed by cardiac magnetic resonance (CMR) predict the prognosis in patients with DCM. METHODS: The present study included patients with DCM and sinus rhythm who underwent CMR between December 2007 and April 2018. LA volume was measured using CMR. LA sphericity index was computed as the ratio of the measured maximum LA volume by the volume of a sphere with maximum LA length diameter. RESULTS: We included 255 patients in this study. During the mean follow-up of 3.92 years, hospitalization for HF occurred in 37 patients. The LA sphericity index was significantly higher in patients with hospitalization for HF than in those without (0.78 ± 0.35 vs. 0.58 ± 0.18, p < .001). Multivariable Cox regression analysis identified a higher LA sphericity index as an independent predictor of hospitalization for HF. Patients were categorized based on the median of LA sphericity index. The Kaplan-Meier curve showed that patients with a high LA sphericity index (≥0.57) had a significantly higher risk of hospitalization for HF than those with a low LA sphericity index (<0.57). CONCLUSION: LA sphericity index was an independent predictor of hospitalization for HF. Assessment of LA geometric parameters might be useful for risk stratification in patients with DCM.