Lymphocyte to monocyte ratio-based nomogram for predicting outcomes of hepatocellular carcinoma treated with sorafenib.

BACKGROUND: The ability of the pretreatment lymphocyte to monocyte ratio (LMR) to predict outcomes of patients with hepatocellular carcinoma (HCC) receiving sorafenib is not conclusively determined. METHODS: We retrospectively studied patients treated with sorafenib for HCC in two tertiary referral centres in Asia and North America. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Predictive factors for the outcomes were determined by Cox proportional hazards models. A risk assessment tool was developed. RESULTS: Compared to the North America cohort, the Asia cohort was more heavily pretreated (72.1% vs. 35.2%; p < 0.001), had higher hepatitis B virus infection (87.6% vs. 5.6%; p < 0.001), and more distant metastases (83.2% vs. 25.4%; p < 0.001). Lower monocyte count in the Asia cohort (median 462.7 vs. 600.0/µL; p = 0.023) resulted in a higher LMR (median 2.6 vs. 1.8; p < 0.001). High LMR was associated with a significantly higher OS [hazard ratio (HR) 0.88; 95% confidence interval (CI) 0.81‒0.97; p = 0.007]. This was confirmed in a sensitivity analysis including patients treated in Asia only (HR 0.89; 95% CI 0.81‒0.97; p = 0.010). An OS nomogram was constructed with the following variables selected in the multivariate Cox model: LMR, treatment location, previous treatment, performance status, alpha-fetoprotein, lymph node metastasis, and Child‒Pugh score. The concordance score was 0.71 (95% CI, 0.67‒0.75). LMR did not predict PFS. CONCLUSION: LMR measured before sorafenib administration predicts OS in advanced HCC patients. Our OS nomogram, incorporating LMR, can be offered to clinicians to improve their ability to assess prognosis, strengthen the prognosis-based decision-making, and inform patients in the clinic.

Outcomes of Anticoagulation Therapy in Adults With Tetralogy of Fallot.

Background Available outcomes data for anticoagulation therapy in adults with congenital heart disease ( CHD ) provide assessment of global risk of this therapy for CHD patients (a heterogeneous population), but the risk of complications for the different CHD diagnoses is unknown. The purpose of the study was to describe the indications for anticoagulation, and the incidence and risk factors for major bleeding complication in adults with tetralogy of Fallot. Methods and Results We queried Mayo Adult Congenital Heart Disease (MACHD) database for tetralogy of Fallot patients (aged ≥18 years) that received anticoagulation, 1990-2017. Of 130 patients (42±14 years, 75 men [58%]), warfarin and direct oral anticoagulants were used in 125 (96%) and 5 (4%), respectively because atrial arrhythmias (n=109), mechanical prosthetic valve (n=29), intracardiac thrombus (n=4), pulmonary embolism (n=6), stroke (n=3), and perioperative anticoagulation (n=44). The median hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score for the entire cohort was 1 (0-2) and 27 (21%) had hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2. There were 14 minor bleeding events (1.6% per year) and 11 major bleeding events (1.3% per year) in 8 patients during median follow-up of 74 months (856 patient-years). Mechanical prosthesis (hazard ratio 1.78, CI 1.29-3.77, P=0.021) and hypertension, abnormal renal or liver function; stroke; bleeding history or predisposition; labile international normalized ratio; elderly (>65 years); drug or alcohol use score ≥2 (hazard ratio 1.41, CI 1.03-3.88, P=0.046) were risk factors for major bleeding events. All-cause mortality was higher in patients with major bleeding events (n=6, 75%) compared with patients without major bleeding events (n=25, 21%), P=0.001. Conclusions Considering the heterogeneity of the CHD population, data from the current study may be better suited for clinical decision-making in tetralogy of Fallot patients.

Use of mechanical valve prostheses in adults with tetralogy of Fallot.

BACKGROUND: There are limited data about the outcomes mechanical prostheses in adults with tetralogy of Fallot (TOF). The purpose of the study was to describe the incidence of mechanical valve related adverse events (MVRAE), reoperation and all-cause mortality in TOF patients with mechanical valve prostheses. METHODS: We reviewed the MACHD (Mayo Adult Congenital Heart Disease) database and identified all adult TOF patients with mechanical valve prostheses, 1990-2017. MVRAE was defined as valve thrombosis, endocarditis, embolic stroke or major bleeding complications. RESULTS: A total of 44 prostheses were implanted in 29 patients (age 44 ±â€¯13 years; men 18 [62%]), and 10 (36%) patients received multiple mechanical prostheses. The median number of prior sternotomies was 3 (range 2-7). Target intentional normalized ratio (INR) was 2.0-3.0 for patients with isolated mechanical aortic prostheses (n = 12, 41%), 2.5-4.0 for mechanical prostheses in non-aortic positions. There were no surgical deaths, and 10 MVRAE (endocarditis [n = 4], major bleeding complications [n = 5] and valve thrombosis [n = 1]) occurred in 7 (24%) patients during a median follow-up of 11 (5 18) years. The 10-year survival and freedom from reoperation were 87% and 95% respectively. CONCLUSIONS: Surgical mortality and valve thrombosis for mechanical valve prostheses are low presumably due to appropriate patient selection and meticulous anticoagulation. Endocarditis and bleeding complications are major concerns. Further studies are required to determine the appropriate target INR that provides the optimal balance between preventing valve thrombosis and avoiding major bleeding complications mechanical valve prostheses in different positions.

Aortic disease and interventions in adults with tetralogy of Fallot.

BACKGROUND: Aortic dilation and aortic valve disease are known long-term complication of tetralogy of Fallot (TOF), but the risk of aortic dissection and the indications for prophylactic aortic surgery are unknown in this population. The purpose of this study was to: (1) determine the prevalence of significant aortic valve disease and/or significant aortic aneurysm (AVD-AA); (2) determine the incidence of progressive aortic dilation and aortic dissection in patients with TOF. METHODS: Retrospective review of adults with repaired TOF, and no prior aortic valve/aorta surgery, who had ≥2 measurements of the thoracic aorta >12 months apart, 1990-2017. The aortic root and mid-ascending aorta were measured at the onset of QRS complex from leading edge to leading edge. Significant aortic valve disease was defined as the presence of ≥moderate aortic stenosis and/or ≥moderate aortic regurgitation. Significant aortic aneurysm was defined as aortic root or mid-ascending aorta dimension ≥50 mm. Progressive aortic dilation was defined as increase in aortic dimension ≥2 mm. RESULTS: Of the 453 consecutive patients (37±13 years, men 216 (49%)) in the study, aortic aneurysm was present in 312 (69%) based on normative data; progressive aortic dilation occurred in 40 (9%), and there was no case of aortic dissection. Significant AVD-AA occurred in 52 (12%) patients; and 15 of them (29%) underwent aortic surgery without any surgical mortality. CONCLUSIONS: Although aortic aneurysm was common, progressive aortic dilation was uncommon and aortic dissection did not occur in our patients with TOF with significant aortic aneurysms who did not undergo aortic surgery. This has important clinical implication in deciding the frequency of imaging follow-up and timing of surgical intervention in this population.

Cardiac implantable electronic devices in adults with tetralogy of Fallot.

BACKGROUND: Tachyarrhythmias and bradyarrhythmias affect 20%-50% of adult patients with tetralogy of Fallot (TOF) and some of these patients will require cardiac implantable electronic devices (CIED) such as pacemaker and/or internal cardioverter defibrillator. METHODS: The Mayo Adult Congenital Heart Disease database was queried for patients with repaired TOF and history of CIED implantation, 1990-2017. The study objectives were: (1) determine the occurrence of device-related complications defined as lead failure, lead recall, device infection and lead thrombus; and (2) determine the occurrence and risk factors for defibrillator shock. RESULTS: There were 99 patients (age 46±14 years and 66 (66%) men) with CIED, and the CIEDs were 41 (41%) pacemakers and 73 (73%) defibrillators. Indication for defibrillator implantation was for primary prevention in 28 (38%) and secondary prevention in 45 (62%). Device-related complications occurred in 20 (20%) patients (lead failure 17, lead recall 4, device infection 12 and thrombus 3). Twenty-five per cent of all device infections occurred within 30 days from the time of device generator change. Annualised rates of appropriate and inappropriate shocks were 5.7% and 6.2%, respectively. The use of class III antiarrhythmic drug was protective against defibrillator shock. CONCLUSION: The current study provides useful outcome data to aid patient counselling and clinical decision-making. Further studies are required to explore ways to decrease the risk of postprocedural infection after device generator change, and to determine which patients will benefit from empirical antiarrhythmic therapy as a strategy to decrease incidence of inappropriate defibrillator shock.

Role of QRS Fragmentation for Risk Stratification in Adults With Tetralogy of Fallot.

Background Patients with tetralogy of Fallot ( TOF ) remain at risk for cardiovascular events despite successful repair. Some of the current risk stratification tools require advanced imaging and invasive studies, and hence are difficult to apply to routine patient care. A recent study showed that QRS fragmentation ( QRS -f) is predictive of mortality in patients with TOF. The current study aims to validate this result by assessing whether severity of QRS -f could predict all-cause mortality in a different TOF population. Methods and Results The authors reviewed the Mayo Adult Congenital Heart Disease database for patients with TOF who had ECG from 1990-2017. QRS -f was defined as notches in QRS complex in ≥2 contiguous leads on ECG , not related to bundle branch block, and classified as none, mild (≤3 leads), moderate (4 leads), or severe (≥5 leads). Of 465 patients (age 37±14 years) in the study, QRS -f was present in 161 (35%): mild (n=43, 9%), moderate (n=77, 17%), and severe (n=41, 9%). There were 55 deaths (12%) during 13.6±8.2 years of follow-up. Severity of QRS -f remained an independent predictor of all-cause mortality after adjustment for other ECG parameters, patient demographics, and atrial and ventricular arrhythmia (hazard ratio, 1.74 per class; 95% confidence interval, 1.08-2.93 [ P=0.041]). Conclusions The presence of severe QRS -f may be used as complementary data to the usual clinical indices to determine whether interventions such as invasive electrophysiology study should be performed in patients with nonsustained ventricular tachycardia or to proceed with pulmonary valve replacement in patients with severe pulmonary regurgitation with ventricular volumes below the guideline-directed threshold for intervention.