Clinical Implications of High-Sensitivity Cardiac Troponin Measurements in Hospitalized Medical Patients

Background

The increased use of high sensitivity cardiac troponins (hs-cTn), have made the diagnosis of non-ST elevation myocardial infarction (MI) challenging, especially in complex medical patients, in whom the clinical presentation of MI is nonspecific and multiple comorbidities as well as non-ischemic acute conditions may account for elevated hs-cTn levels. The aim of this study was to assess the frequency of both elevated hs-cTn levels and dynamic changes in hospitalized patients.

Methods and Findings

We conducted a retrospective study identifying all patients hospitalized in the Internal Medicine Division of Rabin Medical Center, Israel between January 2011 to December 2011, for whom at least one hs-cTn T (hs-cTnT) measurement was obtained. Collected data included patient demographics, acute and chronic diagnosis, hs-cTnT and creatinine levels and date of death. Hs-cTnT levels were obtained in 5,696 admissions and was above the 99th percentile (> = 13 ng/L) in 61.6% of the measurements. A relative change of 50% or higher was observed in 24% of the admissions. Among those with elevated hs-cTnT levels, acute coronary syndromes (ACS) accounted for only 6.1% of acute diagnoses. Maximal hs-cTnT levels above 100 ng/L but not dynamic changes discriminated between ACS and non-ACS conditions (positive and negative predictive values of 12% and 96% respectively). The frequency of elevated hs-cTnT levels was age-dependent and over 75% of patients aged >70 years-old had levels above the 99th percentile. Multivariate analysis identified hs-cTnT levels higher than the 99th percentile, as an independent, strong predictor for 30-day mortality (OR 4.58 [2.8, 7.49], p<0.0001).

Conclusions

Elevated hs-cTnT levels together with dynamic changes are frequent findings among hospitalized patients and in most cases, are not related to the ACS diagnosis. These findings highlight the diagnostic challenge of ACS in this complex population. Further studies are needed in order to optimize the use of hs-cTnT measurements in hospitalized patients.     

Orthostatic Blood Pressure Test for Risk Stratification in Patients with Hypertrophic Cardiomyopathy

Background

Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in young adults, mainly ascribed to ventricular tachycardia (VT). Assuming that VT is the major cause of (pre-) syncope in HCM patients, its occurrence is essential for SCD risk stratification and primarily preventive ICD-implantation. However, evidence of VT during syncope is often missing. As the differentiation of potential lethal causes for syncope such as VT from more harmless reasons is crucial, HCM patients were screened for orthostatic dysregulation by using a simple orthostatic blood pressure test.

Methods

Over 15 months (IQR [9;20]) 100 HCM patients (55.8±16.2 yrs, 61% male) were evaluated for (pre-)syncope and VT (24h-ECGs, device-memories) within the last five years. Eighty patients underwent an orthostatic blood pressure test. Logistic regression models were used for statistical analysis.

Results

In older patients (>40 yrs) a positive orthostatic test result increased the chance of (pre-) syncope by a factor of 63 (95%-CI [8.8; 447.9], p<0.001; 93% sensitivity, 95%-CI [76; 99]; 74% specificity, 95%-CI [58; 86]). No correlation with VT was shown. A prolonged QTc interval also increased the chance of (pre-) syncope by a factor of 6.6 (95%-CI [2.0; 21.7]; p=0.002).

Conclusions

The orthostatic blood pressure test is highly valuable for evaluation of syncope and presyncope especially in older HCM patients, suggesting that orthostatic syncope might be more relevant than previously assumed. Considering the high complication rates due to ICD therapies, this test may provide useful information for the evaluation of syncope in individual risk stratification and may help to prevent unnecessary device implantations, especially in older HCM patients.     

High-Sensitivity Cardiac Troponin Concentrations in Patients with Chest Discomfort: Is It the Heart or the Kidneys As Well?

BackgroundHigh-sensitivity cardiac troponins (hs-cTn) are the preferred biomarkers to detect myocardial injury, making them promising risk-stratifying tools for patients with symptoms of chest pain. However, circulating hs-cTn are also elevated in other conditions like renal dysfunction, complicating appropriate interpretation of low-level hs-cTn concentrations.MethodsA cross-sectional analysis was performed in 1864 patients with symptoms of chest discomfort from the cardiology outpatient department who underwent cardiac computed tomographic angiography (CCTA). Serum samples were analyzed using hs-cTnT and hs-cTnI assays. Renal function was measured by the estimated glomerular filtration rate (eGFR), established from serum creatinine and cystatin C. On follow-up, the incidence of adverse events was assessed.ResultsMedian hs-cTnT and hs-cTnI concentrations were 7.2(5.8–9.2) ng/L and 2.6(1.8–4.1) ng/L, respectively. Multivariable regression analysis revealed that both assay results were more strongly associated with eGFR (hs-cTnT:stβ:-0.290;hs-cTnI:stβ:-0.222) than with cardiac imaging parameters, such as coronary calcium score, CCTA plaque severity score and left ventricular mass (all p<0.01). Furthermore, survival analysis indicated lower relative risks in patients with normal compared to reduced renal function for hs-cTnT [HR(95%CI), 1.02(1.00–1.03) compared to 1.07(1.05–1.09)] and hs-cTnI [1.01(1.00–1.01) compared to 1.02(1.01–1.02)] (all p<0.001).ConclusionIn patients with chest discomfort, we identified an independent influence of renal function on hs-cTn concentrations besides CAD, that affected the association of hs-cTn concentrations with adverse events. Estimating renal function is therefore warranted when interpreting baseline hs-cTn concentrations.     

Observational Cohort Study of Ventricular Arrhythmia in Adults with Marfan Syndrome Caused by FBN1 Mutations

Background

Marfan syndrome is associated with ventricular arrhythmia but risk factors including FBN1 mutation characteristics require elucidation.

Methods and Results

We performed an observational cohort study of 80 consecutive adults (30 men, 50 women aged 42±15 years) with Marfan syndrome caused by FBN1 mutations. We assessed ventricular arrhythmia on baseline ambulatory electrocardiography as >10 premature ventricular complexes per hour (>10 PVC/h), as ventricular couplets (Couplet), or as non-sustained ventricular tachycardia (nsVT), and during 31±18 months of follow-up as ventricular tachycardia (VT) events (VTE) such as sudden cardiac death (SCD), and sustained ventricular tachycardia (sVT). We identified >10 PVC/h in 28 (35%), Couplet/nsVT in 32 (40%), and VTE in 6 patients (8%), including 3 with SCD (4%). PVC>10/h, Couplet/nsVT, and VTE exhibited increased N-terminal pro–brain natriuretic peptide serum levels(P<.001). All arrhythmias related to increased NT-proBNP (P<.001), where PVC>10/h and Couplet/nsVT also related to increased indexed end-systolic LV diameters (P = .024 and P = .020), to moderate mitral valve regurgitation (P = .018 and P = .003), and to prolonged QTc intervals (P = .001 and P = .006), respectively. Moreover, VTE related to mutations in exons 24–32 (P = .021). Kaplan–Meier analysis corroborated an association of VTE with increased NT-proBNP (P<.001) and with mutations in exons 24–32 (P<.001).

Conclusions

Marfan syndrome with causative FBN1 mutations is associated with an increased risk for arrhythmia, and affected persons may require life-long monitoring. Ventricular arrhythmia on electrocardiography, signs of myocardial dysfunction and mutations in exons 24–32 may be risk factors of VTE.     

Low Potassium Dialysate as a Protective Factor of Sudden Cardiac Death in Hemodialysis Patients with Hyperkalemia

AimHyperkalemia increases the risk of sudden cardiac death (SCD) in hemodialysis patients. Our objective was to determine the association between administering low potassium dialysate to hyperkalemic hemodialysis patients and SCD.MethodsWe conducted a retrospective cohort study with patients undergoing maintenance hemodialysis from May 1, 2006, through December 31, 2013. The dialysate composition was adjusted over time according to monthly laboratory results. A 1.0 mEq/L potassium dialysate was applied in patients with predialysis hyperkalemia (>5.5 mEq/L) and was included as a time-dependent confounding factor. The clinical characteristics of enrolled patients, the incidence and timing of SCD and risk factors for all-cause mortality and SCD were analyzed.ResultsThere were 312 patients on maintenance hemodialysis during the study period. One hundred and fifty-seven patients had been dialyzed against a 1.0 mEq/L potassium dialysate at least once. The rates of all-cause mortality and SCD were 48.17 and 20.74 per 1000 patient-years, respectively. A 1.12-fold increase in the risk of SCD in the 24-hour period starting with the hemodialysis procedure and a 1.36-fold increase in the 24 hours preceding a weekly cycle were found (p = 0.017). Multivariate Cox proportional hazards models showed that age, diabetes mellitus and predialysis hyperkalemia (>5.0 mEq/L) were significant predictors of all-cause mortality and SCD. Exposure to 1.0 mEq/L potassium dialysate, Kt/V, and serum albumin were independent protective factors against all-cause mortality. Only exposure to 1.0 mEq/L potassium dialysate significantly prevented SCD (hazard ratio = 0.33, 95% CI = 0.13–0.85).ConclusionsUsing low potassium dialysate in hyperkalemic hemodialysis patients may prevent SCD.     

Pro-Arrhythmic Potential of Oral Antihistamines (H1): Combining Adverse Event Reports with Drug Utilization Data across Europe

Background

There is appreciable utilisation of antihistamines (H₁) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in ’90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines.

Aim

To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries.

Methods

We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance.

Results

Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible.

Conclusions

Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by analytical studies is required, regulators and clinicians should consider risk-minimisation activities. Also antihistamines without signal but with peculiar use in a few Countries (e.g., levocetirizine) or with increasing consumption (e.g., rupatadine) deserve careful surveillance.     

Risk and Outcome after Ablation of Isthmus-Dependent Atrial Flutter in Elderly Patients

MethodsA total of 1187 patients with a mean age 65±12 years consecutively referred for AFL ablation were retrospectively analyzed in the study.Results445 (37.5%) patients were aged ≥70 (range 70 to 93) among which 345 were aged 70 to 79 years (29.1%) and 100 were aged ≥80 (8.4%). In multivariable analysis, AFL-related rhythmic cardiomyopathy and presentation with 1/1 AFL were less frequent (respectively adjusted OR = 0.44, 0.27–0.74, p = 0.002 and adjusted OR = 0.29, 0.16–0.52, p<0.0001). AFL ablation-related major complications were more frequent in patients ≥70 although remained lower than 10% (7.4% in ≥70 vs. 4.2% in <70, adjusted OR = 1.74, 1.04–2.89, p = 0.03). After 2.1±2.7 years, AFL recurrence was less frequent in patients ≥70 (adjusted OR = 0.54, 0.37–0.80, p = 0.002) whereas atrial fibrillation (AF) occurrence was as frequent in the 70–79 and ≥80 age subsets. As expected, cardiac mortality was higher in older patients. Patients aged ≥80 also had a low probability of AFL recurrence (5.0%) and AF onset (19.0%).ConclusionsOlder patients represent 37.5% of patients referred for AFL ablation and displayed a <10% risk of ablation-related complications. Importantly, AFL recurrences were less frequent in patients ≥70 while AF occurrence was as frequent as in patients <70. Similar observations were made in patients ≥80 years. AFL ablation appears to be safe and efficient and should not be ruled out in elderly patients.     

Urine Albumin Excretion Is Associated with Cardiac Troponin T Detected with a Highly Sensitive Assay in a Community-Based Population

Background

Urine albumin excretion is an important predictor of adverse cardiovascular events. Minimally elevated levels of serum cardiac troponin T (cTnT), a marker of cardiomyocyte micronecrosis, can be detected with high sensitivity cTnT (hs-cTnT) assays. The purpose of this study was to investigate the relationship between alterations in albuminuria and serum hs-cTnT levels in a community-based population.

Methods

We examined the association between the urine albumin/creatinine ratio (UACR) and hs-cTnT levels in 1354 participants without overt cardiovascular disease in a community-based, cross-sectional study in Beijing, China.

Results

With the highly sensitive assay, cTnT levels were detectable in 90.5% of our subjects. The median (interquartile range) concentrations of hs-cTnT were 7 (5–10) pg/mL. After adjustment for several factors, UACR (odds ratio: 1.40; 95% confidence interval: 1.08–1.65; P = 0.002) was associated with a higher likelihood of elevated hs-cTnT (≥14 pg/ mL), whereas the relationship between UACR and a higher presence of detectable hs-cTnT (≥ 3 pg/ mL) was not significant. In addition, a fully adjusted logistic regression analysis revealed that compared with participants in the lowest UACR quartile, those in the highest quartile had a 2.43- fold (95% CI: 1.25–5.08; P = 0.006) increased risk of elevated hs-cTnT.

Conclusions

Higher urine albumin excretion is associated with elevated hs-cTnT among persons without clinically evident cardiovascular disease, suggesting that albuminuria may be a potential risk factor for subclinical cardiovascular disease in the general population.     

High-sensitivity cardiac troponin T: risk stratification tool in patients with symptoms of chest discomfort

Background

Recent studies have demonstrated the association between increased concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and the incidence of myocardial infarction, heart failure, and mortality. However, most prognostic studies to date focus on the value of hs-cTnT in the elderly or general population. The value of hs-cTnT in symptomatic patients visiting the outpatient department remains unclear. The aim of this study was to investigate the prognostic value of hs-cTnT as a biomarker in patients with symptoms of chest discomfort suspected for coronary artery disease and to assess its additional value in combination with other risk stratification tools in predicting cardiac events.

Methods

We studied 1,088 patients (follow-up 2.2±0.8 years) with chest discomfort who underwent coronary calcium scoring and coronary CT-angiography. Traditional cardiovascular risk factors and concentrations of hs-cTnT, N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) were assessed. Study endpoint was the occurrence of late coronary revascularization (>90 days), acute coronary syndrome, and cardiac mortality.

Results

Hs-cTnT was a significant predictor for the composite endpoint (highest quartile [Q4]>6.7 ng/L, HR 3.55; 95%CI 1.88–6.70; P<0.001). Survival analysis showed that hs-cTnT had significant predictive value on top of current risk stratification tools (Chi-square change P<0.01). In patients with hs-cTnT in Q4 versus P<0.01). This was not the case for hsCRP and NT-proBNP.

Conclusions

Hs-cTnT is a useful prognostic biomarker in patients with chest discomfort suspected for coronary artery disease. In addition, hs-cTnT was an independent predictor for cardiac events when corrected for cardiovascular risk profiling, calcium score and CT-angiography results.     

Outcomes of Acute Chest Syndrome in Adult Patients with Sickle Cell Disease: Predictors of Mortality

Adults with sickle cell disease(SCD) are a growing population. Recent national estimates of outcomes in acute chest syndrome(ACS) among adults with SCD are lacking. We describe the incidence, outcomes and predictors of mortality in ACS in adults. We hypothesize that any need for mechanical ventilation is an independent predictor of mortality.

Methods

We performed a retrospective analysis of the Nationwide Inpatient Sample(2004–2010),the largest all payer inpatient database in United States, to estimate the incidence and outcomes of ACS needing mechanical ventilation(MV) and exchange transfusion(ET) in patients >21 years. The effects of MV and ET on outcomes including length of stay(LOS) and in-hospital mortality(IHM) were examined using multivariable linear and logistic regression models respectively. The effects of age, sex, race, type of sickle cell crisis, race, co-morbid burden, insurance status, type of admission, and hospital characteristics were adjusted in the regression models.

Results

Of the 24,699 hospitalizations, 4.6% needed MV(2.7% for <96 hours, 1.9% for ≥96 hours), 6% had ET, with a mean length of stay(LOS) of 7.8 days and an in-hospital mortality rate(IHM) of 1.6%. There was a gradual yearly increase in ACS hospitalizations that needed MV(2.6% in 2004 to 5.8% in 2010). Hb-SS disease was the phenotype in 84.3% of all hospitalizations. After adjusting for a multitude of patient and hospital related factors, patients who had MV for <96 hours(OR = 67.53,p<0.01) or those who had MV for ≥96 hours(OR = 8.73,p<0.01) were associated with a significantly higher odds for IHM when compared to their counterparts. Patients who had MV for ≥96 hours and those who had ET had a significantly longer LOS in-hospitals(p<0.001).

Conclusion

In this large cohort of hospitalized adults with SCD patients with ACS, the need for mechanical ventilation predicted higher mortality rates and increased hospital resource utilization. Identification of risk factors may enable optimization of outcomes.     

Plasma Free Hemoglobin Is an Independent Predictor of Mortality among Patients on Extracorporeal Membrane Oxygenation Support

Background

Hemolysis is common in all extracorporeal circuits as evident by the elevated plasma free hemoglobin (PFHb) level. We investigated whether increased hemolysis during extracorporeal membrane oxygenation (ECMO) is an independent mortality predictor.

Methods

We performed a retrospective observational study of consecutive subjects who received ECMO at a tertiary care facility from 2007-2013 to investigate independent predictors of in-hospital mortality. We examined variables related to patient demographics, comorbidities, markers of hemolysis, ECMO characteristics, transfusion requirements, and complications. 24-hour PFHb> 50 mg/dL was used as a marker of severe hemolysis.

Results

154 patients received ECMO for cardiac (n= 115) or pulmonary (n=39) indications. Patients’ mean age was 51 years and 75.3% were males. Compared to nonsurvivors, survivors had lower pre-ECMO lactic acid (p=0.026), lower 24-hour lactic acid (p=0.023), shorter ECMO duration (P=0.01), fewer RBC transfusions on ECMO (p=0.008) and lower level of PFHb 24-hours post ECMO implantation (p=0.029). 24-hour PFHb> 50 mg/dL occurred in 3.9 % versus 15.5% of survivors and nonsurvivors, respectively, p=0.002. A Cox proportional hazard analysis identified PFHb> 50 mg/dL 24-hours post ECMO as an independent predictor of mortality (OR= 3.4, 95% confidence interval: 1.3 – 8.8, p= 0.011).

Conclusion

PFHb> 50 mg/dL checked 24-hour post ECMO implantation is a useful tool to predict mortality. We propose the routine checking of PFHb 24-hours after ECMO initiation for early identification and treatment of the cause of hemolysis.     

Cardiac risk stratification in cancer patients: A longitudinal patient–patient network analysis

BackgroundCardiovascular disease is a leading cause of death in general population and the second leading cause of mortality and morbidity in cancer survivors after recurrent malignancy in the United States. The growing awareness of cancer therapy–related cardiac dysfunction (CTRCD) has led to an emerging field of cardio-oncology; yet, there is limited knowledge on how to predict which patients will experience adverse cardiac outcomes. We aimed to perform unbiased cardiac risk stratification for cancer patients using our large-scale, institutional electronic medical records.Methods and findingsWe built a large longitudinal (up to 22 years’ follow-up from March 1997 to January 2019) cardio-oncology cohort having 4,632 cancer patients in Cleveland Clinic with 5 diagnosed cardiac outcomes: atrial fibrillation, coronary artery disease, heart failure, myocardial infarction, and stroke. The entire population includes 84% white Americans and 11% black Americans, and 59% females versus 41% males, with median age of 63 (interquartile range [IQR]: 54 to 71) years old.We utilized a topology-based K-means clustering approach for unbiased patient–patient network analyses of data from general demographics, echocardiogram (over 25,000), lab testing, and cardiac factors (cardiac). We performed hazard ratio (HR) and Kaplan–Meier analyses to identify clinically actionable variables. All confounding factors were adjusted by Cox regression models. We performed random-split and time-split training-test validation for our model.We identified 4 clinically relevant subgroups that are significantly correlated with incidence of cardiac outcomes and mortality. Among the 4 subgroups, subgroup I (n = 625) has the highest risk of de novo CTRCD (28%) with an HR of 3.05 (95% confidence interval (CI) 2.51 to 3.72). Patients in subgroup IV (n = 1,250) had the worst survival probability (HR 4.32, 95% CI 3.82 to 4.88). From longitudinal patient–patient network analyses, the patients in subgroup I had a higher percentage of de novo CTRCD and a worse mortality within 5 years after the initiation of cancer therapies compared to long-time exposure (6 to 20 years). Using clinical variable network analyses, we identified that serum levels of NT-proB-type Natriuretic Peptide (NT-proBNP) and Troponin T are significantly correlated with patient’s mortality (NT-proBNP > 900 pg/mL versus NT-proBNP = 0 to 125 pg/mL, HR = 2.95, 95% CI 2.28 to 3.82, p < 0.001; Troponin T > 0.05 μg/L versus Troponin T ≤ 0.01 μg/L, HR = 2.08, 95% CI 1.83 to 2.34, p < 0.001). Study limitations include lack of independent cardio-oncology cohorts from different healthcare systems to evaluate the generalizability of the models. Meanwhile, the confounding factors, such as multiple medication usages, may influence the findings.ConclusionsIn this study, we demonstrated that the patient–patient network clustering methodology is clinically intuitive, and it allows more rapid identification of cancer survivors that are at greater risk of cardiac dysfunction. We believed that this study holds great promise for identifying novel cardiac risk subgroups and clinically actionable variables for the development of precision cardio-oncology.

Yuan Hou and co-workers investigate risk of cardiac dysfunction in cancer patients.     

The kinetics of highly sensitive cardiac troponin T release after prolonged treadmill exercise in adolescent and adult athletes

The nature and kinetics of postexercise cardiac troponin (cTn) appearance is poorly described and understood in most athlete populations. We compared the kinetics of high-sensitivity cTn T (hs-cTnT) after endurance running in training-matched adolescents and adults. Thirteen male adolescent (mean age: 14.1 ± 1.1 yr) and 13 male adult (24.0 ± 3.6 yr) runners performed a 90-min constant-load treadmill run at 95% of ventilatory threshold. Serum hs-cTnT levels were assessed preexercise, immediately postexercise, and at 1, 2, 3, 4, 5, 6, and 24 h postexercise. Serum NH(2)-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels were recorded preexercise and 3, 6, and 24 h postexercise. Left ventricular function was assessed preexercise, immediately postexercise, and 6 h postexercise. Peak hs-cTnT occurred at 3-4 h postexercise in all subjects, but was substantially higher (P < 0.05) in adolescents [median (range): 211.0 (11.2-794.5) ng/l] compared with adults [median (range): 19.1 (9.7-305.6) ng/l]. Peak hs-cTnT was followed by a rapid decrease in both groups, although adolescent data had not returned to baseline at 24 h. Substantial interindividual variability was noted in peak hs-cTnT, especially in the adolescents. NT-pro-BNP was significantly elevated postexercise in both adults and adolescents and remained above baseline at 24 h in both groups. In both groups, left ventricular ejection fraction and the ratio of early-to-atrial peak Doppler flow velocities were significantly decreased immediately postexercise. Peak hs-cTnT was not related to changes in ejection fraction, ratio of early-to-atrial peak Doppler flow velocities, or NT-pro-BNP. The present data suggest that postexercise hs-cTnT elevation 1) occurred in all runners, 2) peaked 3-4 h postexercise, and 3) the peak hs-cTnT concentration after prolonged exercise was higher in adolescents than adults.     

What is The Utility of Electrophysiological Study in Elderly Patients with Syncope and Heart Disease?

BackgroundSyncope in elderly patients with heart disease is a growing problem. Its aetiological diagnosis is often difficult. We intended to investigate the value of the electrophysiological study (EPS) in old patients with syncope and heart disease.MethodsEPS was performed in 182 consecutive patients with syncope and heart disease, among whom 62 patients were ≥75 years old and 120 patients <75.ResultsLeft ventricular ejection fraction was 43.9±11.7% in patients ≥75 and 41.1±12.6% in patients <75. During EPS, induced sustained ventricular arrhythmias were as frequent in both groups (27.4% in patients ≥75 versus 27.5% in patients <75, p=0.99) whereas AV conduction abnormalities were more frequent in older patients (37.1% in patients ≥75 versus 18.3% in patients<75, p<0.005). Syncope remained unexplained in 35.5% of patients ≥75 and in 51.7% of patients <75 (p<0.04). ICD was more likely to be implanted in younger patients than in patients ≥75 years (37.5% vs 21% respectively, p<0.009). During a mean follow-up period of 3.3±3 years, the 4-year-survival rate was 66.9±6.8 % in patients ≥75 and 75.9±6.2 % in patients <75 years. The main cause of death was heart failure in both groups. The factors related to a worse outcome in a multivariate analysis were low LVEF and higher age.ConclusionComplete EPS allows the identification of treatable causes in a high proportion of elderly patients with syncope and heart disease. Yet, the prognosis of these patients is mainly related to LVEF and age.     

Improvement of Left Ventricular Function under Cardiac Resynchronization Therapy Goes along with a Reduced Incidence of Ventricular Arrhythmia

Objectives

The beneficial effects of cardiac resynchronization therapy (CRT) are thought to result from favorable left ventricular (LV) reverse remodeling, however CRT is only successful in about 70% of patients. Whether response to CRT is associated with a decrease in ventricular arrhythmias (VA) is still discussed controversially. Therefore, we investigated the incidence of VA in CRT responders in comparison with non-responders.

Methods

In this nonrandomized, two-center, observational study patients with moderate-to-severe heart failure, LV ejection fraction (LVEF) ≤35%, and QRS duration >120 ms undergoing CRT were included. After 6 months patients were classified as CRT responders or non-responders. Incidence of VA was compared between both groups by Kaplan-Meier analysis and Cox regression analysis. ROC analysis was performed to determine the aptitude of LVEF cut-off values to predict VA.

Results

In total 126 consecutive patients (64±11years; 67%male) were included, 74 were classified as responders and 52 as non-responders. While the mean LVEF at baseline was comparable in both groups (25±7% vs. 24±8%; P = 0.4583) only the responder group showed an improvement of LVEF (36±6% vs. 24±7; p<0.0001) under CRT. In total in 56 patients VA were observed during a mean follow-up of 28±14 months, with CRT responders experiencing fewer VA than non-responders (35% vs. 58%, p<0.0061). Secondary preventive CRT implantation was associated with a higher likelihood of VA. As determined by ROC analysis an increase of LVEF by >7% was found to be a predictor of a significantly lower incidence of VA (AUC = 0.606).

Conclusions

Improvement of left ventricular function under cardiac resynchronization therapy goes along with a reduced incidence of ventricular arrhythmia.     

Impact of D-Dimer for Prediction of Incident Occult Cancer in Patients with Unprovoked Venous Thromboembolism

BackgroundUnprovoked venous thromboembolism (VTE) is related to a higher incidence of occult cancer. D-dimer is clinically used for screening VTE, and has often been shown to be present in patients with malignancy. We explored the predictive value of D-dimer for detecting occult cancer in patients with unprovoked VTE.MethodsWe retrospectively examined data from 824 patients diagnosed with deep vein thrombosis or pulmonary thromboembolism. Of these, 169 (20.5%) patients diagnosed with unprovoked VTE were selected to participate in this study. D-dimer was categorized into three groups as: <2,000, 2,000–4,000, and >4,000 ng/ml. Cox regression analysis was employed to estimate the odds of occult cancer and metastatic state of cancer according to D-dimer categories.ResultsDuring a median 5.3 (interquartile range: 3.4–6.7) years of follow-up, 24 (14%) patients with unprovoked VTE were diagnosed with cancer. Of these patients, 16 (67%) were identified as having been diagnosed with metastatic cancer. Log transformed D-dimer levels were significantly higher in those with occult cancer as compared with patients without diagnosis of occult cancer (3.5±0.5 vs. 3.2±0.5, P-value = 0.009, respectively). D-dimer levels >4,000 ng/ml was independently associated with occult cancer (HR: 4.12, 95% CI: 1.54–11.04, P-value = 0.005) when compared with D-dimer levels <2,000 ng/ml, even after adjusting for age, gender, and type of VTE (e.g., deep vein thrombosis or pulmonary thromboembolism). D-dimer levels >4000 ng/ml were also associated with a higher likelihood of metastatic cancer (HR: 9.55, 95% CI: 2.46–37.17, P-value <0.001).ConclusionElevated D-dimer concentrations >4000 ng/ml are independently associated with the likelihood of occult cancer among patients with unprovoked VTE.     

Sudden death and its predictors in myocardial infarction survivors in an Indian population

ObjectiveThis study was conducted to assess the incidence of sudden cardiac death (SCD) in post myocardial infarction patients and to determine the predictive value of various risk markers in identifying cardiac mortality and SCD.MethodsLeft ventricular function, arrhythmias on Holter and microvolt T wave alternans (MTWA) were assessed in patients with prior myocardial infarction and ejection fraction ≤ 40%. The primary outcome was a composite of cardiac death and resuscitated cardiac arrest during follow up. Secondary outcomes included total mortality and SCD.ResultsFifty-eight patients were included in the study. Eight patients (15.5%) died during a mean follow-up of 22.3 ± 6.6 months. Seven of them (12.1%) had SCD. Among the various risk markers studied, left ventricular ejection fraction (LVEF) ≤ 30% (Hazard ratio 5.6, 95% CI 1.39 to 23) and non-sustained ventricular tachycardia (NSVT) in holter (5.7, 95% CI 1.14 to 29) were significantly associated with the primary outcome in multivariate analysis. Other measures, including QRS width, heart rate variability, heart rate turbulence and MTWA showed no association.ConclusionsAmong patients with prior myocardial infarction and reduced left ventricular function, the rate of cardiac death was substantial, with most of these being sudden cardiac death. Both LVEF ≤30% and NSVT were associated with cardiac death whereas only LVEF predicted SCD. Other parameters did not appear useful for prediction of events in these patients. These findings have implications for decision making for the use of implantable cardioverter defibrillators for primary prevention in these patients.     

Elevated Steady State WBC and Platelet Counts Are Associated with Frequent Emergency Room Use in Adults with Sickle Cell Anemia

Introduction

Sickle cell anemia has many sequelae that result in emergency department (ED) use, but a minority of patients with sickle cell disease are frequent utilizers and make up the majority of ED visits. If patients who are likely to be frequent ED can be identified in steady state, they can be treated with disease modifying agents in an attempt to reduce ED use frequency. We sought to identify steady state markers for frequent ED use.

Methods

We identified all patients with SS/Sβ0 seen at our facilities in 2012. Health care utilization over the entire year was calculated and ED visit numbers categorized as either 0–1, 2–5, or 6 or more visits a year. Steady state and acutely active laboratory parameters were collected and analyzed using analysis of variance models and odds ratios.

Results

432 adult sickle cell patients were identified, ages 18–87, 54% female, and 38% had been prescribed hydroxyurea. Of the 432 patients,192 had 0–1 visits in the year, 144 had 2–5 visits in the year, and 96 had >6 visits for a total of 2259 visits. Those who had >6 visits accounted for 1750 (77%) of the total visits for the year. When steady state laboratory markers were examined, each additional 50x109/L platelets was associated with 22% greater risk (p < .001); each 1x109/L of WBC was associated with 11% greater risk (p = .003), and each 1g/dL Hb was associated with 23% lower risk (p = .007) of >6 ED visits/year. We did not observe a relationship between baseline HbF, LDH or reticulocyte count with >6 ED visits.

Conclusion

Patients with elevated white blood cell counts, elevated platelet counts, and low hemoglobin levels exhibited higher risk for frequent ED utilization and could be candidates for early and aggressive therapy with disease modifying agents.