Category: Cardiology

Hot Topics: Algorithm Predicts Irregular Heartbeats

Jackie Werner Cardiology, Hot Topics in Research

A New Prediction Model for Ventricular Arrhythmias in Arrhythmogenic Right Ventricular Cardiomyopathy

Bhonsale A, Murray B, Tichnell C, et al. A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy. . 2019.

Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.

Methods and Results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44–9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73–0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92–0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001).

Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (

Hot Topics: Botox May Help Aftermath of Cardiac Surgery

Jackie Werner Cardiology, Hot Topics in Research, Surgery

Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: Three-year follow-up of a randomized study

Romanov A, Pokushalov E, Ponomarev D, et al. Long-term suppression of atrial fibrillation by botulinum toxin injection into epicardial fat pads in patients undergoing cardiac surgery: Three-year follow-up of a randomized study. Heart Rhythm. 2018.

Botulinum toxin (BTX) injections into epicardial fat pads in patients undergoing coronary artery bypass grafting (CABG) has resulted in suppression of atrial fibrillation (AF) during the early postoperative period through 1-year of follow-up in a pilot program.

The purpose of this study was to report 3-year AF patterns by the use of implantable cardiac monitors (ICMs).

Sixty patients with a history of paroxysmal AF and indications for CABG were randomized 1:1 to either BTX or placebo injections into 4 posterior epicardial fat pads. All patients received an ICM with regular follow-up for 3 years after surgery. The primary end point of the extended follow-up period was incidence of any atrial tachyarrhythmia after 30 days of procedure until 36 months on no antiarrhythmic drugs. The secondary end points included clinical events and AF burden.

At the end of 36 months, the incidence of any atrial tachyarrhythmia was 23.3% in the BTX group vs 50% in the placebo group (hazard ratio 0.36; 95% confidence interval 0.14–0.88; P = .02). AF burden at 12, 24, and 36 months was significantly lower in the BTX group than in the placebo group: 0.22% vs 1.88% ( P = .003), 1.6% vs 9.5% ( P < .001), and 1.3% vs 6.9% ( P = .007), respectively. In the BTX group, 2 patients (7%) were hospitalized during follow-up compared with 10 (33%) in the placebo group ( P = .02).

Injection of BTX into epicardial fat pads in patients undergoing CABG resulted in a sustained and substantial reduction in atrial tachyarrhythmia incidence and burden during 3-year follow-up, accompanied by reduction in hospitalizations.

Hot Topics: Assessment Identifies Patients At Risk for Cardiac-Induced PTSD

Jackie Werner Cardiology, Hot Topics in Research, Psychology and Psychiatry

Development and Validation of a Measure to Assess Patients’ Threat Perceptions in the Emergency Department

Cornelius T, Agarwal S, Garcia O, Chaplin W, Edmondson D, Chang BP. Development and validation of a measure to assess patients’ threat perceptions in the emergency department. Acad Emerg Med. 2018;0.


Threat perceptions in the Emergency Department (ED) (e.g., patients’ subjective feelings of helplessness or lack of control) during evaluation for an acute coronary syndrome (ACS) are associated with the development of posttraumatic stress disorder (PTSD), and PTSD has been associated with medication nonadherence, cardiac event recurrence, and mortality. This study reports the development and validation of a 7‐item measure of ED Threat Perceptions in English‐ and Spanish‐speaking patients evaluated for ACS.


Participants were drawn from an observational cohort study of 1,000 patients evaluated for ACS between 2013‐2016 in a large, New York City hospital. Participants reported on threat perceptions in the ED and during inpatient stay (using 12 items previously identified as predictive of PTSD) and reported on cardiac‐induced PTSD one month post‐discharge. Exploratory and confirmatory factor analyses were used to establish the factor structure and test measurement invariance. Validity and reliability were examined, as was the association of ED Threat Perceptions with cardiac‐induced PTSD.


Factor analyses identified a 7‐item measure of ED Threat Perceptions (e.g., “I feel helpless,” “I am worried that I am going to die”) for both English‐ and Spanish‐speaking patients. ED Threat Perceptions demonstrated convergent validity, correlating with ED stress and ED crowdedness (rs = .29, .14), good internal consistency (α = .82), and stability (r = .61). Threat Perceptions were associated with cardiac‐induced acute stress at inpatient and PTSD symptoms at one month (rs = .43, .39).


This brief tool assessing ED Threat Perceptions has clinical utility for providers to identify patients at risk for developing cardiac‐induced PTSD and is critical to inform research on whether threat may be modified in‐ED to reduce PTSD incidence.

Hot Topics: AI Model Better Predicts Heart Disease Deaths

Jackie Werner Cardiology, Hot Topics in Research

Machine learning models in electronic health records can outperform conventional survival models for predicting patient mortality in coronary artery disease

Steele AJ, Denaxas SC, Shah AD, Hemingway H, Luscombe NM. Machine learning models in electronic health records can outperform conventional survival models for predicting patient mortality in coronary artery disease. PLOS ONE. 2018;13(8):e0202344.

Prognostic modelling is important in clinical practice and epidemiology for patient management and research. Electronic health records (EHR) provide large quantities of data for such models, but conventional epidemiological approaches require significant researcher time to implement. Expert selection of variables, fine-tuning of variable transformations and interactions, and imputing missing values are time-consuming and could bias subsequent analysis, particularly given that missingness in EHR is both high, and may carry meaning. Using a cohort of 80,000 patients from the CALIBER programme, we compared traditional modelling and machine-learning approaches in EHR. First, we used Cox models and random survival forests with and without imputation on 27 expert-selected, preprocessed variables to predict all-cause mortality. We then used Cox models, random forests and elastic net regression on an extended dataset with 586 variables to build prognostic models and identify novel prognostic factors without prior expert input. We observed that data-driven models used on an extended dataset can outperform conventional models for prognosis, without data preprocessing or imputing missing values. An elastic net Cox regression based with 586 unimputed variables with continuous values discretised achieved a C-index of 0.801 (bootstrapped 95% CI 0.799 to 0.802), compared to 0.793 (0.791 to 0.794) for a traditional Cox model comprising 27 expert-selected variables with imputation for missing values. We also found that data-driven models allow identification of novel prognostic variables; that the absence of values for particular variables carries meaning, and can have significant implications for prognosis; and that variables often have a nonlinear association with mortality, which discretised Cox models and random forests can elucidate. This demonstrates that machine-learning approaches applied to raw EHR data can be used to build models for use in research and clinical practice, and identify novel predictive variables and their effects to inform future research.

Hot Topics: Genetic Cause of Final Blood Group System Discovered

Jackie Werner Blood, Cardiology, Hot Topics in Research

Disruption of a GATA1-binding motif upstream of XG/PBDX abolishes Xga expression and resolves the Xg blood group system

Möller M, Lee YQ, Vidovic K, et al. Disruption of a GATA1-binding motif upstream of XG/PBDX abolishes Xga expression and resolves the Xg blood group system. Blood. 2018.

The Xga blood group is differentially expressed on erythrocytes from males and females. The underlying gene, PBDX, was identified already in 1994 but the molecular background for Xga expression remains undefined. This gene, now designated XG, partly resides in the pseudoautosomal region 1 and encodes a protein of unknown function from the X chromosome. By comparing calculated Xgaallele frequencies in different populations to 2,612 genetic variants in the XG region, rs311103 showed the strongest correlation to the expected distribution. The same SNP had the most significant impact on XG transcript levels in whole blood (P=2.0×10-22). The minor allele, rs311103C, disrupts a GATA-binding motif 3.7 kb upstream of the transcription start point. This silences erythroid XG-mRNA expression and causes the Xg(a–) phenotype, a finding corroborated by SNP genotyping in 119 blood donors. Binding of GATA1 to biotinylated oligonucleotide probes with rs311103G but not rs311103C was observed by EMSA and proven by mass spectrometry. Finally, a luciferase reporter assay indicated this GATA motif to be active for rs311103G but not rs311103C in HEL cells. By using an integrated bioinformatics and molecular biology approach, we elucidated the underlying genetic basis for the last unresolved blood group system and made Xga genotyping possible.

Hot Topics: Gut Bacteria May Change Course of Atherosclerosis

Jackie Werner Cardiology, Hot Topics in Research

Metabolic Products of the Intestinal Microbiome and Extremes of Atherosclerosis

Bogiatzi C, Gloor G, Allen-Vercoe E, et al. Metabolic products of the intestinal microbiome and extremes of atherosclerosis. Atherosclerosis. 2018;273:91-97. doi:

Background and aims
There is increasing awareness that the intestinal microbiome plays an important role in human health. We investigated its role in the burden of carotid atherosclerosis, measured by ultrasound as total plaque area.

Multiple regression with traditional risk factors was used to identify three phenotypes among 316/3056 patients attending vascular prevention clinics. Residual score (RES; i.e. the distance off the regression line, similar to standard deviation) was used to identify the 5% of patients with much less plaque than predicted by their risk factors (Protected, RES <−2), the 90% with about as much plaque as predicted (Explained, RES -2 to 2), and the 5% with much more plaque than predicted (Unexplained RES >2). Metabolic products of the intestinal microbiome that accumulate in renal failure – gut-derived uremic toxins (GDUT) – were assayed in plasma by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry.

Plasma levels of trimethylamine n-oxide (TMAO), p-cresyl sulfate, p-cresyl glucuronide, and phenylacetylglutamine were significantly lower among patients with the Protected phenotype, and higher in those with the Unexplained phenotype, despite no significant differences in renal function or in dietary intake of nutrient precursors of GDUT. In linear multiple regression with a broad panel of risk factors, TMAO (p = 0.011) and p-cresyl sulfate (p = 0.011) were significant independent predictors of carotid plaque burden.

The intestinal microbiome appears to play an important role in atherosclerosis. These findings raise the possibility of novel approaches to treatment of atherosclerosis such as fecal transplantation and probiotics.

Hot Topics: New Guidelines Lower Threshold for High Blood Pressure

Jackie Werner Cardiology, Hot Topics in Research

Potential U.S. Population Impact of the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline

Muntner, P., Carey, R. M., Gidding, S., Jones, D. W., Taler, S. J., Wright, J. T., & Whelton, P. K. (2017). Potential U.S. population impact of the 2017 American Ccollege of Cardiology/American Heart Association high blood pressure guideline. Journal of the American College of Cardiology. doi: 10.1016/j.jacc.2017.10.073

Background The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults provides recommendations for the definition of hypertension, systolic and diastolic blood pressure (BP) thresholds for initiation of antihypertensive medication and BP target goals.

Objective Determine the prevalence of hypertension, implications of recommendations for antihypertensive medication and prevalence of BP above the treatment goal among US adults using criteria from the 2017 ACC/AHA and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7) guidelines.

Methods We analyzed data from the 2011-2014 National Health and Nutrition Examination Survey (N=9,623). NHANES participants completed study interviews and an examination. For each participant, blood pressure was measured three times following a standardized protocol and averaged. Results were weighted to produce US population estimates.

Results According to the 2017 ACC/AHA and JNC7 guidelines, the overall crude prevalence of hypertension among US adults was 45.6% (95% confidence interval [CI] 43.6%,47.6%) and 31.9% (95%CI 30.1%, 33.7%), respectively, and antihypertensive medication was recommended for 36.2% (95%CI 34.2%, 38.2%) and 34.3% (32.5%, 36.2%) of US adults, respectively. Compared to US adults recommended antihypertensive medication by JNC7, those recommended treatment by the 2017 ACC/AHA guideline but not JNC7 had higher CVD risk. Non-pharmacological intervention is advised for the 9.4% of US adults with hypertension according to the 2017 ACC/AHA guideline who are not recommended antihypertensive medication. Among US adults taking antihypertensive medication, 53.4% (95%CI 49.9%, 56.8%) and 39.0% (95%CI 36.4%, 41.6%) had BP above the treatment goal according to the 2017 ACC/AHA and JNC7 guidelines, respectively. Overall, 103.3 (95%CI 92.7, 114.0) million US adults had hypertension according to the 2017 ACC/AHA guideline of whom 81.9 (95%CI 73.8, 90.1) million were recommended antihypertensive medication.

Conclusion Compared with the JNC 7 guideline, the 2017 ACC/AHA guideline results in a substantial increase in the prevalence of hypertension but a small increase in the percentage of U.S. adults recommended antihypertensive medication. A substantial proportion of US adults taking antihypertensive medication is recommended more intensive BP lowering under the 2017 ACC/AHA guideline.

Hot Topics: Atrial Fibrillation May Be Commonly Undiganosed

Jackie Werner Cardiology, Hot Topics in Research

Incidence of Previously Undiagnosed Atrial Fibrillation Using Insertable Cardiac Monitors in a High-Risk Population: The REVEAL AF Study

Reiffel JA, Verma A, Kowey PR, al e. Incidence of previously undiagnosed atrial fibrillation using insertable cardiac monitors in a high-risk population: The reveal af study. JAMA Cardiology. 2017.

Importance  In approximately 20% of atrial fibrillation (AF)–related ischemic strokes, stroke is the first clinical manifestation of AF. Strategies are needed to identify and therapeutically address previously undetected AF.

Objective  To quantify the incidence of AF in patients at high risk for but without previously known AF using an insertable cardiac monitor.

Design, Setting, and Participants  This prospective, single-arm, multicenter study was conducted from November 2012 to January 2017. Visits took place at 57 centers in the United States and Europe. Patients with a CHADS2 score of 3 or greater (or 2 with at least 1 additional risk factor) were enrolled. Approximately 90% had nonspecific symptoms potentially compatible with AF, such as fatigue, dyspnea, and/or palpitations.

Exposures  Patients underwent monitoring with an insertable cardiac monitor for 18 to 30 months.

Main Outcomes and Measures  The primary end point was adjudicated AF lasting 6 or more minutes and was assessed at 18 months. Other analyses included detection rates at points from 30 days to 30 months and among CHADS2 score subgroups. Median time from insertion to detection and the percentage of patients subsequently prescribed oral anticoagulation therapy was also determined.

Results  A total of 446 patients were enrolled; 233 (52.2%) were male, and the mean (SD) age was 71.5 (9.9) years. A total of 385 patients (86.3%) received an insertable cardiac monitor, met the primary analysis cohort definition, and were observed for a mean (SD) period of 22.5 (7.7) months. The detection rate of AF lasting 6 or more minutes at 18 months was 29.3%. Detection rates at 30 days and 6, 12, 24, and 30 months were 6.2%, 20.4%, 27.1%, 33.6%, and 40.0%, respectively. At 18 months, AF incidence was similar among patients with CHADS2 scores of 2 (24.7%; 95% CI, 17.3-31.4), 3 (32.7%; 95% CI, 23.8-40.7), and 4 or greater (31.7%; 95% CI, 22.0-40.3) (P = .23). Median (interquartile) time from device insertion to first AF episode detection was 123 (41-330) days. Of patients meeting the primary end point, 13 (10.2%) had 1 or more episodes lasting 24 hours or longer, and oral anticoagulation therapy was prescribed for 72 patients (56.3%).

Conclusions and Relevance  The incidence of previously undiagnosed AF may be substantial in patients with risk factors for AF and stroke. Atrial fibrillation would have gone undetected in most patients had monitoring been limited to 30 days. Further trials regarding the value of detecting subclinical AF and of prophylactic therapies are warranted.

Hot Topics: Cardiovascular Event Risk Lowered by Reducing Inflammation Alone

Jackie Werner Cardiology, Hot Topics in Research

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017.


Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.


We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.


At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31).


Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS number, NCT01327846.)

Hot Topics: Anti-Statin Internet Trend Could Threaten Lives

Jackie Werner Cardiology, Hot Topics in Research

Statin Denial: An Internet-Driven Cult With Deadly Consequences

Nissen SE. Statin Denial: An Internet-Driven Cult With Deadly Consequences. Ann Intern Med. doi: 10.7326/M17-1566

The reduction in cardiovascular morbidity and mortality during the past 3 decades represents one of the great triumphs of contemporary medicine. In 1987, the age-adjusted mortality rate in the U.S. population for cardiovascular disease was 357 in 100 000, decreasing to 167 in 100 000 by 2014 (1). Although precisely gauging the relative contributions of various public health measures to the decline in cardiovascular morbidity and mortality is impossible, most critical observers consider the introduction of statins in 1987 to be one of the keys to this success. According to the Centers for Disease Control and Prevention, the prevalence of elevated low-density lipoprotein cholesterol levels (>4.1 mmol/L [160 mg/dL], >3.4 mmol/L [130 mg/dL], and >2.6 mmol/L [100 mg/dL] for low-, medium-, and high-risk persons, respectively) declined from 59% to 28% between 1980 and 2010 (2). Average low-density lipoprotein cholesterol levels decreased from 3.3 mmol/L (129 mg/dL) in 1988 to 1994 to 3.0 mmol/L (116 mg/dL) in 2007 to 2010.