The effect of off-label use of reduced-dose direct oral anticoagulants therapy in the treatment of pulmonary embolism comparable to standard-dose therapy.

Direct oral anticoagulants (DOACs) have been shown to be effective and safe in preventing pulmonary embolism recurrence. In this single-center retrospective observational study, we aimed to evaluate the efficacy and safety of reduced-dose DOACs in 86 consecutive patients with acute pulmonary embolism. Patients were divided into standard-dose and reduced-dose DOACs groups. Initial clot volume did not significantly differ between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 18.8 [Q1-Q3 7.3-30.8] mL vs. 10.0 [Q1-Q3 3.2-27.9] mL, p = 0.1). Follow-up computed tomography (CT) within 30 days showed a higher rate of clot volume reduction or disappearance in the standard-dose group compared to the reduced-dose group (standard-dose DOACs vs. reduced-dose DOACs, 81.6% vs. 53.9%, p = 0.02). However, at the final follow-up CT, there was no significant difference in clot volume change between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 91.5% vs. 82.0%, p = 0.19). Major bleeding occurred in two patients in the standard-dose group (4.3%) and three patients in the reduced-dose DOACs group (7.7%) (p = 0.5). In conclusion, while standard-dose DOACs demonstrated superior efficacy in early clot reduction, reduced doses of apixaban and edoxaban showed comparable efficacy and safety profiles in long-term treatment of acute pulmonary embolism in certain patients.

Histopathological characteristics of the arrhythmogenic right ventricular cardiomyopathy presenting the electrocardiographic characteristics with Brugada syndrome.

INTRODUCTION: The histopathological characteristics of the overlapping disease states of Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been fully elucidated. METHODS: A 71-year-old man showed coved-type ST-segment elevation with the right precordial leads, and the echocardiography demonstrated right ventricular (RV) dilatation. After 11 months, he died of a polymorphic VT storm. RESULTS: The pathological tissue demonstrated fibrofatty degeneration in the free wall of the RV outflow tract based on the heart autopsy. CONCLUSION: The overlapping disease states of BrS and ARVC showed histopathological characteristics consistent with ARVC.

Prognostic value of left ventricular dyssynchrony evaluated by gated myocardial perfusion imaging in patients with chronic kidney disease and normal perfusion defect scores.

BACKGROUND: This study aimed to investigate whether indices of left ventricular (LV) dyssynchrony by gated myocardial perfusion SPECT (GMPS) could be useful to predict prognosis in chronic kidney disease (CKD) patients with normal perfusion defect scores. METHODS: One hundred and sixty-seven CKD patients with normal perfusion defect scores on adenosine-stress 201Tl GMPS and no previous history of overt heart diseases were enrolled. Phase standard deviation (PSD) and bandwidth (BW) were automatically calculated from GMPS. The major adverse cardiac events (MACEs) for a mean of 560 days were defined as sudden cardiac death, fatal arrhythmias, and acute coronary syndrome requiring urgent coronary revascularization. Patients were divided into two groups according to the presence or absence of MACEs. RESULTS: The MACEs occurred in 12 patients (7.1%). Patients who experienced MACEs showed significantly higher PSD and wider BW than those who did not. In the Kaplan-Meier event-free survival analysis, cardiac event rate was significantly higher in the high-PSD and wide-BW group (n = 81) than in the low-PSD and narrow-BW group (n = 71) (P = .002). The multivariate regression analysis revealed that the PSD was associated with MACEs (odds ratio 1.33, 95% confidence interval 1.05-1.69, P = .01). CONCLUSION: The LV dyssynchrony indices from GMPS may be novel prognostic predictors in CKD patients with normal perfusion defect scores.

Prognostic impact of mitral L-wave in patients with hypertrophic cardiomyopathy without risk factors for sudden cardiac death.

Hypertrophic cardiomyopathy (HCM) with severe diastolic dysfunction is a major cause of heart failure and sudden cardiac death (SCD) associated with lethal arrhythmia. Although various risk factors for cardiac events have been reported in HCM patients, previous studies have reported that some HCM patients exhibit either no risk or a low risk of SCD experienced cardiac events. The mid-diastolic transmitral flow velocity curve (mitral L-wave) is an echocardiographic index of left ventricular compliance, and it has been reported as one of the parameters of advanced diastolic dysfunction assessed noninvasively. However, little is known about the association between the mitral L-wave and long-term clinical outcomes in HCM patients without SCD risk factors. Between July 2005 and February 2016, 112 patients were diagnosed with HCM and 96 patients without risk factors were enrolled. After excluding 3 patients whom we could not detect L-wave more than once, 93 patients (mean age 57.7 ± 13.1 years, 33 females) were divided into the following two groups, according to the presence or absence of the mitral L-wave: Group L (+) (with the mitral L-wave) and Group L (-) (without the mitral L-wave). The correlations between the mitral L-wave and rates of cardiac events were investigated. The mitral L-wave was present in 14 (15.1%) patients [Group L]. During the follow-up period [4.7 (2.9-7.5) years], patients experienced 7 cardiac events. Kaplan-Meier survival analysis showed that the event-free rate was significantly lower in Group L (+) than in Group L (-) (log-rank P = 0.002). Additionally, in multivariate analysis, L-wave positivity was identified as independent predictors of cardiac events. Existence of the mitral L-wave can predict cardiac events, even in HCM patients without SCD risk factors.

Left ventricular phase entropy: Novel prognostic predictor in patients with dilated cardiomyopathy and narrow QRS.

BACKGROUND: The prognostic impact and pathophysiology of global left ventricular mechanical dyssynchrony (LVMD), namely mechanical dyssynchrony of whole left ventricle, as assessed by phase analysis of electrocardiographically gated (ECG-gated) myocardial perfusion SPECT has not been clearly elucidated in patients with dilated cardiomyopathy (DCM) and narrow QRS complex (<120 ms). METHODS AND RESULTS: Forty-six patients with DCM underwent ECG-gated myocardial 99mTc-sestamibi perfusion SPECT and endomyocardial biopsy. LV phase entropy was automatically calculated using a phase analysis of ECG-gated myocardial perfusion SPECT. The patients were divided into two groups according to the median phase entropy value: low-phase entropy (<0.61) (N = 23: LE group) and high-phase entropy (≥0.61) (N = 23: HE group). In the Kaplan-Meier survival analysis, the event-free survival rate was significantly lower in the HE group (log-rank P = 0.015). Moreover, high-phase entropy was an independent predictor of adverse cardiac events (hazard ratio, 5.77%; 95% confidence interval, 1.02-108.32; P = 0.047). Interestingly, the mRNA expression levels of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) in endomyocardial biopsy specimens were significantly lower in the HE group (P = 0.015). CONCLUSION: LV phase entropy, which may reflect impairment of Ca2+ handling caused by decreased SERCA2a mRNA levels, is a novel prognostic predictor in patients with DCM and narrow QRS complex.

Left ventricular hypertrophy and proteinuria in patients with essential hypertension in Andkhoy, Afghanistan.

Left ventricular hypertrophy (LVH) and proteinuria are known as independent predictors of cardiovascular death in hypertension. However, LVH and its association with proteinuria have not been investigated in adult hypertensive patients in Afghanistan. The objective of this research was to determine the prevalence of LVH and the correlation between LVH and proteinuria among the Afghan adult hypertensive population visiting an outpatient clinic in Afghanistan. We retrospectively evaluated 789 hypertensive patients (mean age is 56 years and 46% were men) who visited the clinic between December 2014 and August 2016. Patient characteristics and laboratory and clinical findings were recorded. The rate of LVH among hypertensive patients was 54.4%. Patients with proteinuria had a significantly higher LVH percentage compared to those without proteinuria (73.2% versus 55.8%; P<0.001). There was a significant correlation between LVH and proteinuria among hypertensive patients (r=0.182, P<0.001). Based on a multivariate regression analysis, age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.05), proteinuria (OR, 1.69; 95% CI, 1.19-2.41), and female sex (OR, 0.09; 95% CI, 0.06-0.13) were significant factors. In conclusion, the prevalence of LVH was more than 50% in the Afghan adult hypertensive population. This study indicates that there is a significant relationship between LVH detected by ECG and the presence of proteinuria among such subjects.

Abnormal Circadian Blood Pressure Profile as a Prognostic Marker in Patients with Nonischemic Dilated Cardiomyopathy.

OBJECTIVES: An abnormal circadian blood pressure (BP) profile is considered a risk factor for cardiovascular disease. However, its significance in heart failure patients with nonischemic etiology is unknown. Herein, we investigated the prognostic value of a circadian BP profile in patients with nonischemic dilated cardiomyopathy (NIDCM). METHODS: We enrolled 114 NIDCM patients (76 males, mean age 53.1 years). The percent nighttime BP fall (%NBPF) was defined using ambulatory BP monitoring as a percent decrease in mean systolic BP in nighttime from daytime. All patients were divided into three groups: dipper (%NBPF ≥10), non-dipper (0 ≤ %NBPF < 10), and riser (%NBPF <0). RESULTS: Riser patients had the highest serum creatinine levels (dipper, 0.78 ± 0.20 mg/dl; non-dipper, 0.85 ± 0.21 mg/dl; riser, 0.99 ± 0.23 mg/dl; p = 0.006). In survival analysis, riser patients had the highest cumulative cardiac-related deaths (log-rank, p = 0.001), which was an independent predictor of cardiac-related deaths (hazard ratio, 12.6; 95% confidence interval, 1.76-253; p = 0.01). Multivariate analysis revealed that the norepinephrine level at 24-hour collected urine (24 h U-NE) and the serum creatinine level were independent determinants of %NBPF (adjusted R2 = 0.20; 24 h U-NE, p = 0.0001; serum creatinine, p = 0.04). CONCLUSIONS: The riser profile was associated with poor prognosis of NIDCM, which may reflect impaired sympathetic nervous system activity. Evaluating the circadian BP profile may be useful for risk stratification in NIDCM patients.

Sokolow-Lyon voltage is suitable for monitoring improvement in cardiac function and prognosis of patients with idiopathic dilated cardiomyopathy.

BACKGROUND: The clinical significance of electrocardiogram in the assessment of patients with idiopathic dilated cardiomyopathy (IDCM) is currently unknown. The aim of this study was to determine the feasibility of recording serial changes in Sokolow-Lyon voltage (∆%QRS-voltage) in one year to estimate left ventricular reverse remodeling (LVRR) and predict a prognosis of IDCM patients under tailored medical therapy. METHODS: Sixty-eight consecutive patients with mild symptoms (52.1 ± 13 years old; 69% men; NYHA I/II/III/IV; 33/29/6/0) underwent electrocardiography and echocardiography at baseline and 12 month follow-up (follow-up period: 3.9 years). RESULTS: LVRR was observed in 30 patients (44.1%). The ∆%QRS-voltage was significantly lower in the LVRR group (LVRR; -26.9%, non-LVRR: -9.2%, p < .001). Univariate analysis showed that ∆%QRS-voltage correlated with ∆%LV end-diastolic diameter (r = .634, p < .001), and with ∆%LV ejection fraction and ∆%LV mass index (r = -.412, p < .001; r = .429, p < .001 respectively). Using receiver operating characteristic curve analysis for the estimation of LVRR, ∆%QRS of -14.7% showed optimal sensitivity (63.2%) and specificity (83.3%) (AUC = 0.775, p < .001). The composite endpoints of cardiac death (n = 0), hospitalization for advanced heart failure (n = 11) and fatal arrhythmia (n = 2) were observed in 13 patients during the follow-up period. Kaplan-Meier analysis showed significantly higher event-free rate in patients of the low ∆%QRS-voltage group (<-14.7%) (83%) than those of the high group (66%, p = .022). CONCLUSIONS: The present study showed that decrease in Sokolow-Lyon voltage is associated with improvement in cardiac function and favorable prognosis in IDCM patients on medical therapy, suggesting that this index is a feasible marker for response to treatment of IDCM.

Associations between proteinuria and cardiovascular risk factors among hypertensive patients in Andkhoy, Afghanistan.

Proteinuria in hypertension is an early marker of renal disease and a predictor for the progression of end stage renal disease, and cardiovascular diseases. This study was designed to determine the prevalence of proteinuria and its association with cardiovascular risk factors among adult hypertensive patients in Afghanistan. Five hundred fifty-five patients with a high blood pressure recorded in an outpatient clinic in Andkhoy, Afghanistan from December 2014 to May 2015, were included in this study. Data obtained from each patient, included demographic characteristics, body mass index, blood pressure patterns, cardiovascular history, cardiovascular risk factors, comorbidity, and current drug-therapy. Dipstick screening for proteinuria was performed with reagent test strips. The mean age of the patients was 57.9 ± 13.3 years, and a female predominance was observed (n = 333, 60%). The prevalence of proteinuria was 67.2%. The predictors of proteinuria were found to be age ≥65 years (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.00-1.04), smoking (OR 1.88, 95% CI 1.17-3.02), heart failure (OR 2.23, 95% CI 1.13-4.41), and diabetes mellitus (OR 3.41, 95% CI 1.49-7.81). In conclusion, this study shows that proteinuria is highly prevalent among hypertensive outpatients in an outpatient clinic in Andkhoy, Afghanistan, especially in those with high cardiovascular risk.

Radiofrequency Ablation of Re-entrant Atrial Tachycardia Originating from the Superior Vena Cava with a High-resolution, 3-dimensional Mapping System.

An 80-year-old man with no previous history of catheter ablation or cardiac surgery underwent catheter ablation for atrial tachycardia (AT). We suspected that the mechanism causing AT was re-entry indicated by the entrainment phenomenon during AT and through activation mapping with a 3-dimensional mapping system (EnSite™ X EP system; Abbott, Chicago, IL, USA). We used a multipolar catheter (Advisor™ HD Grid Mapping Catheter; Abbott) inserted into the superior vena cava (SVC) to accomplish activation mapping. The AT circuit was localized inside the SVC with a fractionated potential recorded on its right lateral wall. A similar fractionated potential was observed in the surrounding area. These areas functioned as the critical isthmus of the AT. Radiofrequency (RF) catheter ablation at these sites eliminated the tachycardia. After RF delivery, no tachycardia was induced by programmed stimulation, even during isoproterenol infusion. Consequently, there was no recurrence of tachycardia even after catheter ablation.

Usefulness of P-wave duration in patients with sick sinus syndrome as a predictor of atrial fibrillation.

BACKGROUND: This study aimed to clarify P-wave duration (PWD) ability before pacemaker implantation to predict worsening atrial fibrillation (AF) burden after the procedure. METHODS: We retrospectively investigated 75 patients who underwent permanent pacemaker implantation due to sick sinus syndrome (SSS) at Komaki City Hospital between January 2006 and May 2019. Worsening AF burden was defined as an increase in the number of AF episodes, each lasting ≥5.5 hours a day. RESULTS: In the study population, 17 patients (23%) had worsening AF burden during the follow-up period. These patients had significantly longer PWD in lead Ⅱ (117.9 ± 19.9 ms vs 101.3 ± 20.0 ms, P = .002) than the patients without worsening AF burden. The best discriminative cutoff value for PWD in lead Ⅱ was 108 ms (sensitivity, 77%; specificity, 67%). In multivariate analysis, PWD in lead II ≥108 ms (hazard ratio, 5.395; 95% confidence interval, 1.352-21.523; P = .017) was an independent predictor of worsening AF burden. Patients with PWD in lead II <108 ms showed a significantly higher event-free rate against worsening AF burden than those with PWD in lead II ≥108 ms (81% vs 9%, P = .005). CONCLUSIONS: Prolonged PWD before pacemaker implantation was the most important independent predictor of worsening AF burden after the procedure. In patients with SSS, prolonged PWD can be a useful marker for predicting worsening of AF burden after pacemaker implantation.

Pathological changes of the myocardium in reworsening of anthracycline-induced cardiomyopathy after explant of a left ventricular assist device.

We herein report the long-term changes in cardiac function and pathological findings after successful explantation of a left ventricular assist device in a 42-year-old patient with anthracycline-induced cardiomyopathy with reworsening heart failure. Endomyocardial biopsy samples revealed that the cardiomyocyte diameter decreased and collagen volume fraction increased just after left ventricular assist device explantation. The collagen volume fraction decreased after 6 months, despite preserved systolic function. At 5 years after left ventricular assist device explantation, the systolic function markedly decreased and cardiomyocyte diameter increased. Pathological changes of the myocardium may enable the identification of cardiac dysfunction prior to echocardiographic changes in patients with reworsening heart failure after left ventricular assist device explantation.

Gatekeeping in an inpatient rehabilitation facility to reduce morbidity and mortality due to cardiac disease: screening program using of BNP and ECG Auto-diagnosis.

The Kaifukuki-Rehabilitation Ward (KRW) is a type of inpatient rehabilitation facility in Japan. In the KRW of our institute, mortality and frequency of emergency referrals in 2013 were rather high, 2.6% and 4.3%, respectively. We aimed to investigate the usefulness of an original gatekeeping system to reduce mortality and morbidity from cardiac complications, and to improve the quality of medical care in the KRW. A total of 370 consecutive patients admitted to the KRW of Kobayashi Memorial Hospital between 1 May 2015 and 31 March 2016 were enrolled in this prospective observational study. All patients underwent a screening evaluation in which we defined patients as being screen positive (SC-positive) if they had at least one of 20 diagnostic ECG codes and/or BNP level over 140 pg/dL at admission. A cardiologist provided weekly interventions to those among SC-positive patients who needed cardiac disease treatment during hospitalization. In all, 129 patients were classified as SC-positive (mean age 80 years, 124 [32%] male), and weekly intervention was needed in 28 patients, including start of cardiac medication in 17 cases. Mortality and frequency of emergency transfer due to cardiac disease during hospital stay were 0.3% and 0.3%, respectively. Our gatekeeping system involving a screening evaluation at admission and weekly intervention in selected patients by a cardiologist may be useful in reducing mortality and rate of transfer due to cardiac disease and may improve quality of medical care in KRWs.

Potential prognostic implications of myocardial thallium-201 and iodine-123-beta-methylpentadecanoic acid dual scintigraphy in patients with Anderson-Fabry disease.

OBJECTIVES: Information on the relationship between myocardial damage assessed by myocardial scintigraphy and prognosis in patients with Anderson-Fabry disease (AFD) is lacking. We therefore aimed to investigate the prognostic impacts of myocardial thallium-201 (201Tl) and iodine-123 beta-methyl 15-para-iodophenyl 3(R, S)-methylpentadecanoic acid (123I-BMIPP) dual scintigraphy in patients with AFD. METHODS: Eighteen consecutive patients with AFD underwent resting myocardial 201Tl/123I-BMIPP dual scintigraphy. Total defect scores (TDS) on both images were calculated visually according to the 17-segment model using a 5-point scoring system. The mismatch score (MS) was calculated as 'TDS on 123I-BMIPP-TDS on 201Tl'. RESULTS: Six major adverse cardiac events (MACEs) were recorded during a mean follow-up of 6.7 ± 4.2 years (three heart failure requiring hospitalization and three cardiac deaths). Left ventricular mass index, left atrial diameter, brain natriuretic peptide, TDS on 123I-BMIPP, and MS were all significantly greater in patients with MACEs compared with those without. Kaplan-Meier analysis indicated that high TDS on 123I-BMIPP and high MS were associated with poor event-free survival. CONCLUSION: TDS on 123I-BMIPP was a better prognostic determinant in patients with AFD than TDS on 201Tl. Myocardial 201Tl/123I-BMIPP dual scintigraphy may thus be a useful noninvasive modality for evaluating prognosis in patients with AFD.

Hemodynamics of cardiac tamponade during extracorporeal membrane oxygenation support in a patient with fulminant myocarditis.

Fulminant myocarditis (FM) causes rapid onset severe heart failure requiring inotropes or mechanical circulatory support. Myocarditis is sometimes associated with pericardial effusion, however, how this effusion affects the hemodynamics in patients with FM under venoarterial extracorporeal membrane oxygenation (VA-ECMO) management has not been fully reported. We show a case of FM presenting with cardiac tamponade during VA-ECMO management. A 64-year-old female diagnosed as having FM showed a rapid hemodynamic collapse and that led to the application of VA-ECMO. Although her left ventricular ejection fraction did not improve despite proper hemodynamics management for several days, a pericardial effusion accumulated gradually. Apparent elevation of right atrial pressure and reduction of blood pressure were not observed, however, we performed pericardiocentesis because we were not able to wean off VA-ECMO. After the drainage of pericardial effusion, the blood pressure and cardiac output elevated as did the left ventricular ejection fraction. We successfully removed VA-ECMO and the patient was discharged without any complications. This is a case report in which a cardiac tamponade under VA-ECMO did not show typical signs and pericardiocentesis contributed to withdrawal of a VA-ECMO system. .

Promising method for management of venoarterial extracorporeal membrane oxygenation: A case of severe heart failure successfully stabilized by "high-flow/vasodilation method".

We report the case of a 58-year-old man with dilated cardiomyopathy who was hospitalized because of worsening heart failure. As his symptoms were refractory even with the administration of inotropes, he was given peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) upon transfer to our hospital. On admission, serum creatinine was 2.62 mg/dL and total bilirubin 10.8 mg/dL. The cannulas inserted were 16-Fr for infusion and 21-Fr for drainage. When the blood flow was increased to 2.14 L/min/m2 to improve organ dysfunction, the aortic valve became continuously close with the mean arterial pressure of 85 mmHg. Therefore, we administrated vasodilators to decrease mean arterial pressure, or left ventricular afterload, which achieved opening aortic valve continuously. After the cannula sizes were scaled up to 18Fr for infusion and 24Fr for drainage to gain further blood flow, the aortic valve opened continuously and mean pulmonary pressure decreased. Our strategy to maintain adequate flow rate of VA-ECMO using vasodilator, "high-flow/vasodilation method", achieved hemodynamic stability. Additionally, the concentration of serum creatinine and total bilirubin gradually decreased to within the normal range, although the patient succumbed 58 days after transfer to our hospital. .

The Selvester QRS score as a predictor of cardiac events in nonischemic dilated cardiomyopathy.

BACKGROUND: Myocardial fibrosis is associated with poor prognosis in nonischemic dilated cardiomyopathy (NIDCM) patients. The Selvester QRS score on 12-lead electrocardiogram is associated with both the amount of myocardial scar and poor prognosis in myocardial infarction patients. However, its use in NIDCM patients is limited. We investigated the prognostic value of the QRS score and its association with collagen volume fraction (CVF) in NIDCM patients. METHODS: We enrolled 91 consecutive NIDCM patients (66 men, 53±13 years) without permanent pacemakers or cardiac resynchronization therapy devices. The Selvester QRS score was calculated by two expert cardiologists at NIDCM diagnosis. All patients were followed up over 4.5±3.2 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening heart failure, and lethal arrhythmia. We also evaluated CVF using endomyocardial biopsy samples. RESULTS: At baseline, the left ventricular ejection fraction was 32±9%, plasma brain natriuretic peptide level was 80 [43-237] pg/mL, and mean Selvester QRS score was 4.1 points. Twenty cardiac events were observed (cardiac death, n=1; hospitalization for worsening heart failure, n=16; lethal arrhythmia, n=3). Cox proportional hazard regression analysis revealed that the Selvester QRS score was an independent determinant of cardiac events (hazard ratio, 1.32; 95% confidence interval, 1.05-1.67; p=0.02). The best cut-off value was determined as 3 points, with 85% sensitivity and 47% specificity (area under the curve, 0.688, p=0.011). In Kaplan-Meier survival analysis, the QRS score ≥3 group had more cardiac events than the QRS score <3 group (log-rank, p=0.007). Further, there was a significant positive correlation of Selvester QRS score with CVF (r=0.46, p<0.001). CONCLUSIONS: The Selvester QRS score can predict future cardiac events in NIDCM, reflecting myocardial fibrosis assessed by CVF.

Late-Onset Fulminant Myocarditis With Immune Checkpoint Inhibitor Nivolumab.

A 60-year-old man was diagnosed with melanoma. After receiving 13 infusions of nivolumab, he had fulminant myocarditis. The myocardial biopsy specimen revealed extensive lymphocytic infiltration, interstitial edema, and myocardial necrosis, with predominant CD4+, CD8+, CD20-, and programmed death-1- markers. Programmed death-1 ligand 1 (PD-L1) was predominantly expressed on the surface of the damaged myocardium. Although it is reported that myocarditis induced by the human anti-programmed death-1 inhibitor nivolumab therapy rarely occurred at > 2 months use in clinical trials, this case showed that even if at a late phase, long-term use of immune checkpoint inhibitors might to lead immune-related adverse events including myocarditis.

Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy.

BACKGROUND: Little is known about whether the alteration of cholesterol metabolism reflects abdominal organ impairments due to heart failure. Therefore, we investigated the prognostic value of cholesterol metabolism by evaluating serum campesterol and lathosterol levels in patients with early-stage nonischemic dilated cardiomyopathy (NIDCM). METHODS: We enrolled 64 patients with NIDCM (median age 57.5 years, 31% female) with New York Heart Association functional class I/II. Serum campesterol and lathosterol levels were measured in all patients. The patients were then divided into four subsets based on the median non-cholesterol sterol levels (campesterol 3.6µg/mL, lathosterol 1.4µg/mL): reference (R-subset), high-campesterol/high-lathosterol; absorption-reduced (A-subset), low-campesterol/high-lathosterol; synthesis-reduced (S-subset), high-campesterol/low-lathosterol; double-reduced (D-subset), low-campesterol/low-lathosterol. Endpoint was a composite of cardiac events, including cardiac-related death, hospitalization for worsening heart failure, and lethal arrhythmia. RESULTS: Median brain natriuretic peptide (BNP) level was 114pg/mL. Mean left ventricular ejection fraction was 31.4%. D-subset had the lowest total cholesterol level and cardiac index and the highest BNP level and pulmonary capillary wedge pressure. D-subset also had the highest cardiac event rate during the mean 3.8 years of follow-up (log-rank p=0.001). Multivariate regression analysis showed that D-subset was an independent determinant of cardiac events. The receiver operating characteristic curve analysis revealed that total cholesterol <153mg/dL was a best cut-off value for discrimination of the D-subset. CONCLUSIONS: The combined reduction of campesterol and lathosterol that indicated intestinal cholesterol absorption and liver synthesis predicts future cardiac events in patients with mildly symptomatic NIDCM.

Myocardial contractile reserve predicts left ventricular reverse remodeling and cardiac events in dilated cardiomyopathy.

BACKGROUND: Catecholamine sensitivity estimated using a dobutamine stress test (DST) is recognized as a measure of the beta-adrenergic myocardial contractile reserve, which is involved with left ventricular reverse remodeling (LV-RR). We investigated whether the prognostic ability of the DST for LV-RR could predict cardiac events. METHODS: There was a total of 192 enrolled patients with dilated cardiomyopathy (DCM). DCM was defined as a LV ejection fraction (LV-EF) ≤45% and LV end-diastolic dimension (LVDd) ≥55mm. One hundred patients were subjected to micromanometer-based measurement of the maximal first derivative of LV pressure (LVdP/dtmax), an index of LV contractility, at baseline and following the infusion of dobutamine (10µg/kg/min) via a pigtail catheter. Percentage changes in LVdP/dtmax from the baseline to peak values under dobutamine stress (ΔLVdP/dtmax) were also calculated. After excluding 17 patients who received cardiac resynchronization therapy within 3 months of undergoing DST (n=15) and who did not receive follow-up echocardiography (n=2), 83 patients were enrolled (52.5±12.3 years). RESULTS: During the follow-up period (4.7±2.6 years), LV-RR was recognized in 49 of 83 patients (59.0%). A multivariate logistic regression analysis revealed that ΔLVdP/dtmax (hazard ratio: 1.024, p=0.007) and the symptom duration (hazard ratio: 0.977, p=0.003) were independent predictors of LV-RR. A receiver operating characteristic curve analysis revealed a ΔLVdP/dtmax cut-off value of 75.1% for LV-RR and a significantly lower cardiac event rate in the ΔLVdP/dtmax≥75.1% group (p=0.045). CONCLUSIONS: ΔLVdP/dtmax estimated using DST was a useful predictor of LV-RR and cardiac events in patients with DCM.