JACC in a Flash

Prevalence of AFib and Atrial Arrhythmias in Congenital Heart Disease Associated With Age

Cardiology Magazine, Jan. 2017

Intra-atrial re-entrant tachycardia (IART) is the most common atrial arrhythmia in patients with congenital heart disease, with significantly higher rates in patients with a more complex disease, according to a study published in the Journal of the American College of Cardiology. However, the study also finds that atrial fibrillation (AFib) increases in prevalence — surpassing IART— and atrial arrhythmias become more permanent as patients age.

In a multicenter cohort study, Fabien Labombarda, MD, et al., assessed the types and patterns of atrial arrhythmias, associated factors and age-related trends in 482 patients with congenital heart disease and atrial arrhythmia across North America. Read More >>>

Among the 482 patients, 54.8 percent were women and the mean age was 32 ± 18 years. The type of congenital heart disease was classified in patients as simple (18.5 percent), moderate (34.4 percent) and complex (47.1 percent).

Results showed the most common arrhythmia was IART at 61.6 percent (mean age, 28.8 ± 16.8 years), followed by AFib at 28.8 percent (mean age, 41.0 ± 17.2 years) and focal atrial tachycardia at 9.5 percent (mean age, 23.6 ± 18.5 years).

The number of arrhythmias from IART increased with congenital heart disease complexity from 47.2 percent to 62.1 percent to 67.0 percent in patients with simple, moderate and complex defects.

"The number of arrhythmias from IART increased with congenital heart disease complexity from 47.2 percent to 62.1 percent to 67.0 percent in patients with simple, moderate and complex defects."

AFib, on the other hand, increased with age and became the most common arrhythmia in those 50 years and older. Out of 136 patients who were at least 50 years old by the end of follow-up, 73 (53.7 percent) had developed AFib.

In multivariable analyses, older age (odds ratio [OR], 1.024 per year; 95 percent confidence interval [CI], 1.010-1.039) and hypertension (OR, 2.00; 95 percent CI, 1.08-3.71) were independently associated with AFib.

Over the course of a mean follow-up of 11.3 ± 9.4 years, the predominant pattern of atrial arrhythmias in patients was paroxysmal in 62.3 percent, persistent in 28.2 percent and permanent in 9.5 percent. Paroxysmal and persistent arrhythmia patterns declined from ages 20 to over 50 years. However, permanent arrhythmias increased with age, from 3.1 percent in patients under 20 years to 5.5 percent, 12.9 percent, and 22.6 percent for ages 20 to 34 years, 35 to 49 years, and 50 years and older.

In an accompanying editorial, Michael J. Silka, MD, and Yaniv Bar-Cohen, MD, comment, “The study provides some useful insights and, perhaps more importantly, raises further questions about the next sequel or possibly series of events as these patients survive into and beyond middle age.” They add, “It becomes critical to define the relative risks for the development of AFib, to determine which specific forms of CHD are associated with the development of AFib, and finally, to establish whether there are therapeutic measures of demonstrable benefit or prevention.”

Labombarda F, Hamilton R, Shohoudi A, et al. J Am Coll Cardiol 2017;70:857-65.

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Association Between Modifiable Risk Factors and Heart Failure in Women With Atrial Fibrillation

Cardiology Magazine, Jan. 2017

Heart failure (HF) is the most common non-fatal event experienced in women with new-onset atrial fibrillation (AFib), and directly modifiable risk factors, such as obesity, hypertension, smoking and diabetes account for the majority of the population risk of HF, according to research published in JACC: Heart Failure.

Study authors Neal A. Chatterjee, MD, MSc, et al., assessed 34,736 women participating in the Women’s Health Study, ages 45 and older, who were free of prevalent cardiovascular disease on study entry. Data analysis showed that new-onset AFib was associated with an increased risk of HF, and once women with AFib developed HF, all-cause and cardiovascular mortality increased. Read More >>>

The combination of systolic blood pressure (SBP) >120 mm Hg, obesity, tobacco use and diabetes mellitus accounted for an estimated 62 percent of population-attributable risk of HF. When compared with women with three to four of these modifiable risk factors, those who achieved or maintained optimal risk factor control benefitted from a progressive decrease in HF risk.

“The onset of AFib has been consistently associated with increased mortality in diverse populations, including those with low cardiovascular disease burden… Despite major advances, improvement in overall survival for patients with AFib has been modest,” write Chatterjee, et al. “Our data provide support for the concept that targeting modifiable risk factors, including obesity, smoking, elevated SBP, and diabetes mellitus, in patients with new-onset AFib has the potential to significantly reduce the individual risk and population burden of HF.” Given its prevalence in patients with AFib, strategies for HF prevention are lacking. Study authors suggest that prospective assessment of risk factor modification at the time of AFib diagnosis may warrant future investigation.

In an editorial comment, Darae Ko, MD, writes, “There is now convincing evidence that HF prevention is an important management priority for patients with AFib. Efforts to reduce HF incidence are critical to reduce the public health burden of AFib. Several large, prospective observational studies have identified potential therapeutic targets of intervention. Pragmatic randomized controlled trials are needed to generate effective evidence-based strategies.”

Chatterjee NA, Chae CU, Kim E, et al. JACC: Heart Failure 2017;5:552-60.

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Cancer Patients at Heightened Risk for Arterial Thromboembolism

Cardiology Magazine, Jan. 2017

Patients with incident cancer have a significantly increased risk of arterial thromboembolism vs. patients without cancer, especially during the first six months after diagnosis, according to a study published August 14 in the Journal of the American College of Cardiology.

Using the Surveillance Epidemiology and End Results (SEER)-Medicare linked database for this retrospective study, Babak B. Navi, MD, MS, et al., assessed newly diagnosed patients with breast, lung, prostate, colorectal, bladder, pancreatic or gastric cancer or non-Hodgkin lymphoma between 2002 to 2011. The cancer patients were individually matched by demographics and comorbidities to a Medicare enrollee without cancer — totaling 279,719 pairs — and followed through 2012. Read More >>>

Among the pairs, median age was 74 years and 48 percent were men. Validated diagnosis codes were used to identify arterial thromboembolism, defined as myocardial infarction (MI) or ischemic stroke. Cumulative incidence rates were calculated using competing risk survival statistics and Cox proportional hazards analysis was used to compare rates between groups at discrete times.

Results showed that the six-month cumulative incidence of arterial thromboembolism was 4.7 percent (95 percent confidence interval [CI], 4.6-4.8 percent) in patients with cancer compared with 2.2 percent (95 percent CI, 2.1-2.2 percent) in patients without cancer (hazard ratio [HR], 2.2; 95 percent CI, 2.1-2.3).

In patients with cancer compared with those without cancer, at six months the cumulative incidence of MI was higher (2.0 percent vs. 0.7 percent; HR, 2.9; 95 percent CI, 2.8-3.1) as well as ischemic stroke (3.0 percent vs. 1.6 percent; HR, 1.9; 95 percent CI, 1.8-2.0).

The investigators also found that excess risk for arterial thromboembolism was higher in patients with later cancer stages and with lung, gastric and pancreatic cancers. However, cancer patients at all stages were at heightened risk.

“These data suggest that cancer is a common risk factor for arterial thromboembolism,” the study authors write. “Future research should investigate the mechanistic basis for these findings, the utility of including cancer in cardiovascular risk prediction models, and optimal strategies to prevent arterial thromboembolism in cancer patients.”

In an accompanying editorial, Edward T.H. Yeh, MD, FACC, and Hui-Ming Chang, MD, MPH, comment, “This paper should not be viewed as merely a big data confirmation of Trousseau Syndrome.” They add, “It is a call to action: for cardiologists to work closely with oncologists to prevent the occurrence of MI or ischemic stroke in cancer patients; and, for interventional cardiologists to take an active role in managing cancer patients with acute MI.”

Navi BB, Reiner AS, Kamel H, et al. J Am Coll Cardiol 2017;70:926-38.

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LCZ696 Prevents Cardiac Rupture, Improves Survival Post AMI in Mice

Cardiology Magazine, Jan. 2017

LCZ696 (sacubitril/valsartan) protects against cardiac rupture and improves survival after acute myocardial infarction (AMI) in mice, according to results presented at ESC Congress 2017 and simultaneously published in JACC: Basic to Translational Science.

The study, led by Koichi Kaikita, MD, PhD, et al., examined the effects of LCZ696 on acute experimental MI in mice and whether it has cardioprotective effects beyond renin-angiotensin-aldosterone system (RAAS) blockade. Mice with a percentage of fractional shortening (%FS) <30 percent at 24 hours after MI were randomized to oral LCZ696 (20 mg/kg/day; n = 75), enalapril (4 mg/kg/day; n = 79) or vehicle (n = 77). Read More >>>

At post-operative day one, no differences in infarct size were seen between groups. The post-MI survival rate was significantly higher with LCZ696 vs. enalapril (p < 0.01) and vehicle (p < 0.01). In most mice (94.8 percent), the cause of death was left ventricular (LV) rupture. With LCZ696, LV rupture was lower vs. enalapril (p < 0.05) and vehicle (p < 0.01).

No differences in fractional shortening, LV end-diastolic dimension or LV end-systolic dimension were observed in any group before and one day after MI. The %FS improved significantly with LCZ696 compared with vehicle at 14 days and 28 days after MI, but did not improve significantly compared with enalapril.

"LCZ696 improved the balance between the RAAS and natriuretic peptide system, prevented cardiac rupture and improved survival after MI, likely due to suppression of proinflammatory cytokines and extracellular matrix degradation in macrophages."

Three days after MI, in the infarcted region, mRNA expression was significantly lower with LCZ696 vs. enalapril for interleukin (IL)-1b, IL-6 and matrix metalloproteinase (MMP)-9, and vs. vehicle for IL-1b, MMP-9 and tissue inhibitors of metalloproteinases (TIMP)-1. In the non-infarcted region, mRNA expression was significantly lower with LCZ696 vs. vehicle for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Immunofluorescence imaging indicated that macrophages might be a main source of MMP-9 in the infarcted myocardium.

With LCZ696, at three days post MI, plasma aldosterone levels were significantly lower vs. vehicle and plasma cyclic GMP (cGMP) levels were higher vs. vehicle and enalapril. The aldosterone/cGMP ratio was significantly lower with LCZ696 vs. vehicle and enalapril.

According to the study investigators, LCZ696 improved the balance between the RAAS and natriuretic peptide system, prevented cardiac rupture and improved survival after MI, likely due to suppression of proinflammatory cytokines and extracellular matrix degradation in macrophages. As a result, they suggest LCZ696 might be useful clinically to improve survival in the acute phase of MI.

Ishii M, Kaikita K, Sato K, et al. JACC Basic Transl Sci 2017;August 28:[Epub ahead of print].

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Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, CHD and Pediatrics and Quality Improvement, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Hypertension, Smoking

Keywords: ACC Publications, Cardiology Magazine, Aged, Aldosterone, Atrial Fibrillation, Atrial Natriuretic Factor, Blood Pressure, Cardiovascular Diseases, Cause of Death, Comorbidity, Confidence Intervals, Cross-Sectional Studies, Cyclic GMP, Cytokines, Diabetes Mellitus, Enalapril, Extracellular Matrix, Fluorescent Antibody Technique, Follow-Up Studies, Heart Conduction System, Heart Defects, Congenital, Heart Failure, Heart Rupture, Hypertension, Incidence, Interleukin-6, Lymphoma, Non-Hodgkin, Macrophages, Matrix Metalloproteinase 9, Medicare, Middle Aged, Myocardial Infarction, Myocardium, Natriuretic Peptide, Brain, Obesity, Pancreatic Neoplasms, Prospective Studies, Prostate, Public Health, Renin-Angiotensin System, Research Personnel, Retrospective Studies, Risk, Risk Factors, RNA, Messenger, Smoking, Stomach Neoplasms, Stroke, Survival Rate, Tachycardia, Supraventricular, Thromboembolism, Tissue Inhibitor of Metalloproteinase-1, Urinary Bladder

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