An exploratory study of effectiveness and safety of rivaroxaban in patients with left ventricular thrombus (R-DISSOLVE).

Evidence on the treatment for left ventricular (LV) thrombus is limited and mainly derives from retrospective studies. The aim of R-DISSOLVE was to explore the effectiveness and safety of rivaroxaban in patients with LV thrombus. R-DISSOLVE was a prospective, interventional, single-arm study, conducted from Oct 2020 to June 2022 at Fuwai Hospital, China. Patients with a history of LV thrombus < 3 months and with systemic anticoagulation therapy < 1 month were included. The thrombus was quantitatively confirmed by contrast-enhanced echocardiography (CE) at baseline and follow-up visits. Eligible patients were assigned to rivaroxaban (20 mg once daily or 15 mg if creatinine clearance was between 30 and 49 mL/min) and its concentration was determined by detecting anti-Xa activity. The primary efficacy outcome was the rate of LV thrombus resolution at 12 weeks. The main safety outcome was the composite of ISTH major and clinically relevant non-major bleeding. A total of 64 patients with complete CE results were analyzed for efficacy outcomes. The mean LV ejection fraction was 25.4 ± 9.0%. The dose-response curve of rivaroxaban was satisfactory based on the peak and trough plasma levels and all concentrations were in the recommended treatment range according to NOAC guidelines. The incidence rate of thrombus resolution at 6 weeks was 66.1% (41/62, 95% CI 53.0-77.7%), and of thrombus resolution or reduction was 95.2% (59/62, 95% CI 86.5-99.0%). At 12 weeks, the thrombus resolution rate was 78.1% (50/64, 95% CI 66.0-87.5%) while the rate of thrombus resolution or reduction was 95.3% (61/64, 95% CI 86.9-99.0%). The main safety outcome occurred in 4 of 75 patients (5.3%) (2 ISTH major bleeding and 2 clinically relevant non-major bleeding). In patients with LV thrombus, we reported a high thrombus resolution rate with acceptable safety by rivaroxaban, which could be a potential option for further LV thrombus treatment.Trial registration This study was registered at ClinicalTrials.gov as NCT04970381.

Impact of levosimendan on efficacy and renal function in acute heart failure according to renal function: A perspective, multi-center, real-world registry.

Objective: Acute heart failure (AHF) is associated with high mortality. Levosimendan, an inodilator, has proved to increase cardiac output and exert renoprotective effect in AHF. Our aim was to investigate the efficacy and renoprotective effects of levosimendan in patients with AHF and different renal function. Methods: This is a prospective, observational, multi-center registry. Patients admitted with AHF between June 2020 and May 2022 and treated with levosimendan during the hospital stay were included. Baseline characteristics, laboratory tests, electrocardiogram (ECG), chest X-ray, echocardiography, and treatment were collected. A 5-point Likert scale was used to document patients' baseline dyspnea. The estimated glomerular filtration rate (eGFR) was calculated by means of the Modification of Diet in Renal Disease equation. After levosimendan infusion, patients underwent assessment of degree of dyspnea, and levels of brain-type natriuretic peptide (BNP) /N-terminal pro-BNP (NT-pro BNP), and eGFR repeatedly. Results: Among 789 AHF patients who received levosimendan treatment in this study, 33.0 % were female, mean age was 64.9 ± 16.8 years, and mean eGFR was 72.6 ± 32.5 ml/min/m2. The mean score of dyspnea was 3.0 ± 1.0 using 5-point Likert scale before levosimendan infusion. Dyspnea improved in 68.7% patients at 6h after infusion of levosimendan, and in 79.5% at 24 h. Lower eGFR was associated with lower efficacy rate after 6h infusion (71.7, 70.7, 65.2, and 66.0%, respectively) and after 24 h infusion (80.5, 81.4, 76.2, and 77.8%, respectively). The levels of BNP or NT-pro BNP were also decreased after levosimendan treatment, and in each eGFR category. Levels of eGFR increased from baseline (72.6 ± 32.5 ml/min/m2) to 12-24h (73.8 ± 33.5 ml/min/m2) and 24-72h (75.0 ± 33.4 ml/min/m2) after starting treatment (p < 0.001). However, the eGFR levels increased only in patients with eGFR lower than 90.0 ml/min/m2. Conclusions: In AHF patients who received levosimendan, degree of dyspnea and levels of BNP or NT-pro BNP were significantly improved, especially in patients with higher eGFR levels. However, levosimendan infusion increase eGFR only in AHF patients with renal dysfunction.

Lymphocytic myocarditis presenting as acute myocardial infarction: a case report and review of the literature.

We report a case that presented as acute myocardial infarction (AMI) caused by lymphocytic myocarditis (LM), and explore the relationship between AMI and LM. We also performed a literature search to identify publications that previously reported LM-associated myocardial infarction. Coronary angiography of our patient revealed normal coronary arteries. However, a perfusion-metabolism mismatch in the apex and mid-inferior walls supported the diagnosis of AMI, and right ventricular septal endomyocardial biopsy showed LM. Extensive viral serological tests were negative for an infectious etiology. Immunosuppressive therapy may be beneficial in patients with high-risk myocarditis who are pathologically confirmed to be virus-negative.

Multiparametric Cardiovascular Magnetic Resonance in Acute Myocarditis: Comparison of 2009 and 2018 Lake Louise Criteria With Endomyocardial Biopsy Confirmation.

Background: Cardiac magnetic resonance (CMR) has been shown to improve the diagnosis of myocarditis, but no systematic comparison of this technique is currently available. The purpose of this study was to compare the 2009 and 2018 Lake Louise Criteria (LLC) for the diagnosis of acute myocarditis using 3.0 T MRI with endomyocardial biopsy (EMB) as a reference and to provide the cutoff values for multiparametric CMR techniques. Methods: A total of 73 patients (32 ± 14 years, 71.2% men) with clinically suspected myocarditis undergoing EMB and CMR with 3.0 T were enrolled in the study. Patients were divided into two groups according to EMB results (EMB-positive and -negative groups). The CMR protocol consisted of cine-SSFP, T2 STIR, T2 mapping, early and late gadolinium enhancement (EGE, LGE), and pre- and post-contrast T1 mapping. Their potential diagnostic ability was assessed with receiver operating characteristic curves. Results: The myocardial T1 and T2 relaxation times were significantly higher in the EMB-positive group than in the EMB-negative group. Optimal cutoff values were 1,228 ms for T1 relaxation times and 58.5 ms for T2 relaxation times with sensitivities of 86.0 and 83.7% and specificities of 93.3 and 93.3%, respectively. The 2018 LLC had a better diagnostic performance than the 2009 LLC in terms of sensitivity, specificity, positive predictive value, and negative predictive value. T1 mapping + T2 mapping had the largest area under the curve (0.95) compared to other single or combined parameters (2018 LLC: 0.91; 2009 LLC: 0.76; T2 ratio: 0.71; EGEr: 0.67; LGE: 0.73; ). The diagnostic accuracy for the 2018 LLC was the highest (91.8%), followed by T1 mapping (89.0%) and T2 mapping (87.7%). Conclusion: Emerging technologies such as T1/ T2 mapping have significantly improved the diagnostic performance of CMR for the diagnosis of acute myocarditis. The 2018 LLC provided the overall best diagnostic performance in acute myocarditis compared to other single standard CMR parameters or combined parameters. There was no significant gain when 2018LLC is combined with the EGE sequence.

Relationship of paraoxonase-1 Q192R genotypes and in-stent restenosis and re-stenting in Chinese patients after coronary stenting.

BACKGROUND AND AIMS: Asians have very different genotype distributions of cytochrome P450 2C19 (CYP2C19), ATP-binding cassette, sub-family B, member 1 (ABCB1), and paraoxonase-1 (PON1), in whom relevant studies based on large samples are scarce. The purpose of this study was to evaluate the effects of these genes on outcomes of in-stent restenosis and re-stenting in Chinese patients after coronary stenting. METHODS: A total of 2569 acute coronary syndrome (ACS) patients were enrolled in a gene database study. Among the 1674 patients receiving coronary stenting, 504 patients performed repeated coronary angiography within the next year after discharge and were eligible to complete our final cohort. RESULTS: The prevalence of the CYP2C19 loss-of-function carriers (had at least 1 allele of *2, *3 and *4) was considerable high (52.2%). During re-angiography, in-stent restenosis occurred in 106 (21.0%) out of the 504 patients; the mean restenosis degree was 71.3% and 152 (30.2%) patients received re-stenting treatment. In multivariate regression, only age and left ventricular ejection fraction (LVEF) were significantly associated with in-stent restenosis. As for predictors of re-stenting, multivariate regression identified variables of LVEF, coronary artery lesions, and PON1 Q192R genotype. Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting compared with genotypes of QQ and QR (OR 1.95, 95% CI 1.30-2.93, p = 0.001). The genotypes of CYP2C19, ABCB1 C3435T, and PON1 L55M showed no significant associations with in-stent restenosis or re-stenting. CONCLUSIONS: Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting in Chinese ACS patients after coronary stenting.

Comparison of 4 Admission Blood Pressure Indexes for Predicting 30-Day Mortality in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: We compared admission systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP) in predicting 30-day all-cause mortality in patients with ST-segment elevation myocardial infarction (STEMI) without cardiogenic shock. METHODS: A retrospective study was performed in 7,033 consecutive STEMI patients. Multivariate-adjusted hazard ratios (HRs) with a 10mm Hg increment and quartiles of each blood pressure were determined by Cox proportional hazard analyses; Wald χ (2) tests were used to compare the strength of relationships. RESULTS: Totally 593 (8.4%) patients died during follow-up. Of 4 indexes, only SBP (HR 0.94 per 10mm Hg, 95% confidence interval (CI) 0.91 to 0.98; P = 0.001) and PP (HR 0.89 per 10 mmHg, 95% CI 0.85 to 0.94; P < 0.001) were significantly associated with 30-day all-cause mortality; these in the highest vs. lowest quartiles of SBP (≥140 vs. <110mm Hg) and PP (≥60 vs. <40mm Hg) had HRs of mortality of 0.70 (95% CI 0.55 to 0.87; P = 0.003) and 0.60 (95% CI 0.47 to 0.75; P < 0.001), respectively. Compared with SBP, PP was a better predictor for mortality no matter in men (χ (2) = 5.9 for per 10mm Hg, χ (2) = 10.8 for quartiles) or women (χ (2) = 15.1 for per 10mm Hg, χ (2) = 19.5 for quartiles), and the relationship remained significant after adjustment of SBP. There was a pattern of declining risk with increasing blood pressures for mortality, and this trend was mainly observed in age groups of more than 70 years. CONCLUSIONS: Pulse pressure was an independent predictor of mortality in patients with STEMI, and low admission blood pressure should serve as a warning sign.

Serum Potassium Levels and Short-Term Outcomes in Patients With ST-Segment Elevation Myocardial Infarction.

Current guidelines recommend maintaining serum potassium levels between 4.0 and 5.0 mEq/L (1 mEq/L = mmol/L) in patients with acute myocardial infarction. However, these guidelines are based on studies conducted before the ß blocker and reperfusion era. We retrospectively analyzed 6613 patients diagnosed with ST-segment elevation myocardial infarction (STEMI) who presented without renal insufficiency. Patients were categorized into 5 groups according to mean serum potassium levels: <3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mEq/L. Patients with potassium levels of 4.0 to <4.5 mEq/L had the lowest predefined event rates, which were 6.4% for 7-day malignant arrhythmia, 3.7% for 7-day mortality, and 5.3% for 30-day mortality. Compared with the reference group (4.0 to <4.5 mEq/L), multivariate regression analysis revealed significantly higher 30-day mortality risk in patients with potassium level of 4.5 to <5.0 (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.17-1.98; P = .002) and even higher risk in patients with potassium level of ≥5.0 mEq/L (HR: 1.80, 95% CI: 1.22-2.66; P = .002). The lowest 30-day mortality was observed in patients with STEMI having potassium levels between 4.0 and 4.5 mEq/L, and a level >4.5 mEq/L significantly increased mortality risk.

Impact of Admission Systolic Blood Pressure and Antecedent Hypertension on Short-Term Outcomes After ST-Segment Elevation Myocardial Infarction: Strobe-Compliant Article.

We evaluated the combined effect of admission systolic blood pressure (SBP) and antecedent hypertension on short-term outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Data were derived from a multicenter survey of 7303 consecutive patients with STEMI. Patients were divided into 4 groups according to different blood pressure status: high SBP without hypertension, high SBP with hypertension, low SBP without hypertension, and low SBP with hypertension. The primary endpoints were 7 and 30-day all-cause mortality. The prevalence of hypertension was 40.7%, and the best cutoff of admission SBP for predicting 30-day mortality was 108 mmHg by receiver-operating characteristic curve. Patients with hypertension were older, more often female, also had longer onset-to-admission time, more comorbidities, and higher Killip class. Patients with both low SBP (≤108 mmHg) and hypertension group had significantly higher 7 and 30-day mortality than those in other groups (all P < 0.001). After multivariate adjustment, low SBP with hypertension group was still an independent risk factor for predicting 7-day mortality (hazard ratios [HR] 1.86, 95% confidence interval [CI] 1.41-2.46; P < 0.001) and 30-day mortality (HR 1.88, 95% CI 1.46-2.43; P < 0.001). In patients with SBP > 108 mmHg, a history of hypertension could increase the risk of 30-day mortality by 27% (HR 1.00 vs 1.27, P = 0.012), while in patients with SBP ≤ 108 mmHg, this increased risk reached to 37% (HR 1.51 vs 1.88, P < 0.001). In conclusion, low admission SBP was the relatively dominant contributor for predicting 7 and 30-day all-cause mortality, and a concurrent antecedent hypertension increased the corresponding risk of mortality.

[Sirolimus use in heart transplantation recipients with chronic renal dysfunction].

OBJECTIVE: To observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction. METHODS: From June 2004 to December 2008, standard calcineurin inhibitors (CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus), and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 - 15 µg/L, and CNI dose was reduced gradually to 1/2-2/3 of the baseline level. Patients were followed for changes in renal function, lipid level and clinical side effects related to immunosuppressive therapy. Endomyocardial biopsy (EMB) was performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation. Echocardiography was performed for monitoring purpose. RESULTS: The mean follow-up after regimen change was (7.9 ± 6.3) months. Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ± 3.8)µg/L. Cyclosporine dose was reduced from (191.7 ± 60.0) mg/d to (123.6 ± 34.8) mg/d, with blood drug concentration reduced from (175.5 ± 58.0) µg/L to (111.9 ± 56.0) µg/L in 18 patients (P < 0.01). Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d, with blood drug concentration reduced from 13.5 µg/L to 10.5 µg/L in 2 patients. Serum creatinine level fell from (160.4 ± 25.5) µmol/L to (134.4 ± 26.8) µmol/L (P < 0.01) and urea nitrogen fell from (13.8 ± 4.7) µmol/L to (10.4 ± 3.0) µmol/L (P < 0.01) at one month after regimen change. Twenty two EMBs were performed in 11 patients within 1 year post-transplant, there were 4 episodes of acute rejected (ISHLT grade 2). Twenty patients are all alive and cardiac function was normal. The most common side effect was hyperlipidemia, and triglycerides, total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change (P < 0.05 or P < 0.01). Leukocyte, hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change (all P > 0.05). CONCLUSION: Our results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction, leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.

[Clopidogrel metabolism related gene polymorphisms in Chinese patients with acute coronary syndrome].

OBJECTIVE: To detect the single nucleotide polymorphisms of clopidogrel metabolism related genes (CYP2C19, ABCB1 and PON1) in Chinese patients with acute coronary syndrome (ACS) by genotype analysis. METHODS: Genetic analysis was performed in patients admitted to Fuwai Hospital from 2005 to 2008 with ACS within 4 weeks. The detection of polymorphisms was performed by TaqMan real-time PCR method. The alleles genotyped were CYP2C19 *2-*8, *17, ABCB1 C3435T, PON1 Q192R and PON1 L55M. Minor allele frequency (MAF) was calculated. Patients were classified as one of the 5 categories by clopidogrel metabolizer phenotypes as extensive [without any "loss-of-function" (LOF) allele *2-*8 or "gain-of-function" (GOF) allele *17], intermediate (with only one LOF allele), Poor (with two or more LOF alleles), ultra (with one or two GOF alleles) or unknown (with one LOF allele and one GOF allele). RESULTS: A total of 2800 ACS patients were enrolled [mean age (59.0 ± 12.3) years and 2236 males (79.9%)]. There were 74% patients with ST-segment elevation myocardial infarction (STEMI, n = 2072), 22.0% patients with non-ST-segment elevation myocardial infarction (NSTEMI, n = 617) and 4.0% patients with unstable angina (UA, n = 111). The minor allele frequency (MAF) for each genotype of CYP2C19 *2, *3, *4, *17 was 28.7%, 4.6%, 0.1% and 1.2%, respectively. There was no LOF allele *5-*8 in the study population. The MAF for ABCB1 C3435T, PON1 Q192R and PON1 L55M was 39.4%, 37.8% and 4.4%, respectively. Clopidogrel metabolizer groups were defined as extensive in 41.7%, intermediate in 45.6%, poor in 10.3%, ultra in 1.9% and unknown in 0.6% patients, respectively. There were no significant differences for all genotypes between males and females. Total LOF carriers of CYP2C19 were 56.4% and GOF carriers were 2.5%. CONCLUSIONS: Our study demonstrated a high distribution of the LOF allele of CYP2C19 in China ACS population.

[Association between serum NT-proBNP/hs-CRP and acute rejection after heart transplantation].

OBJECTIVE: The aim of the present work was to investigate the potential relationship between acute rejection and serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP)/high sensitivity C reactive protein (hs-CRP) in post-transplant patients. METHODS: Sixty-one consecutive orthotopic heart transplantation recipients were prospectively recruited from the cardiac transplantation programme at Fuwai Hospital. Endomyocardial biopsies (EMB) were performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB were also performed when patients had new symptoms of heart failure or at 2 weeks after steroid pulse therapy. Serum NT-proBNP and hs-CRP were simultaneously measured before EMB procedure. RESULTS: A total of 126 biopsy samples were obtained from the 61 patients. Serum NT-proBNP concentrations progressively decreased after transplantation (spearman correlation coefficient -0.520, P = 0.000). NT-proBNP levels within 6 months after transplantation were significantly higher than those beyond 6 months post transplantation [(11.86 +/- 11.16) x 10(-16) mol/L vs.(5.83 +/- 6.58) x 10(-16) mol/L, P = 0.002]. NT-proBNP concentrations in patients with rejection tended to be higher than patients without rejection (13.68 x 10(-16) mol/L vs. 9.26 x 10(-16) mol/L, P = 0.073). After time adjustment, the difference of NT-proBNP concentrations between patients with or without rejection becomes statistically significant (14.45 x 10(-16) mol/L vs. 9.1 x 10(-16) mol/L, P = 0.025). Receiver operating characteristics analysis for NT-proBNP versus rejection grade revealed an area under the curve of 0.566, indicating a low predictive value for NT-proBNP. A cutoff of 6.00 x 10(-16) mol/L yielded poor specificity (44.8%) and sensitivity (57.1%), the sensitivity and specificity were 38.1% and 61.0%, respectively with a cutoff of 8.00 x 10(-16) mol/L. hs-CRP levels within 6 months after transplantation tended to be higher than those beyond 6 months [(2.39 +/- 3.90) mg/L vs. (1.34 +/- 2.73) mg/L, P = 0.069]. hs-CRP concentrations in patients with rejection were similar as patients without rejection (2.995 mg/L vs. 1.833 mg/L, P = 0.138). The incidence of rejection was similar in patients with two higher biomarkers (5/20, 25%) compared to patients with two low biomarkers (3/26, 11.5%, P = 0.232). CONCLUSIONS: NT-proBNP level decreased after transplantation. Although increased NT-proBNP concentrations were related to rejection, the diagnostic capacity was low. Elevated hs-CRP concentrations were not related to rejection after heart transplantation.