JACC in a Flash

Featured topics and Editors' Picks from all of ACC's JACC Journals.

Unique Study Uses Registry Data to Compare TAVR Outcomes in Low-Risk Patients

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TAVR is safe in low-risk patients with symptomatic severe aortic stenosis, based on new research published in the Journal of the American College of Cardiology and presented during ESC Congress 2018. Researchers reported low procedural complication rates, short hospital length of stay, zero mortality and zero disabling stroke at 30 days.

The Low Risk TAVR trial involved 200 low-risk patients with symptomatic severe aortic stenosis undergoing TAVR at 11 U.S. centers. Outcomes from these patients were compared with a cohort of 719 patients from the STS database who underwent SAVR at the same centers.

Findings at 30 days showed all-cause mortality was zero with TAVR compared with 1.7 percent with SAVR. Similarly, in-hospital stroke was zero with TAVR vs. 0.6 percent with SAVR. The rates of new-onset atrial fibrillation (3.0 percent) and length of stay (2.0±1.1days) were low in the TAVR group.

One patient in the TAVR group had greater than mild paravalvular leak at 30 days, while 14 percent of TAVR patients had evidence of subclinical leaflet thrombosis at 30 days. Permanent pacemaker implantation rates were similar in both groups.

"This study is the first prospective study of TAVR in low-risk patients conducted in the U.S. utilizing a historical cohort from a major national database as the control group," noted the study authors. With the ability to randomize patients to surgery likely to become more difficult in the future, this methodology could be increasingly used to evaluate new devices.

Waksman R, Rogers T, Torguson R, et al. J Am Coll Cardiol 2018;Aug 28:[Epub ahead of print].

CAD an Independent Risk Factor For Thromboembolic Events?

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Coronary artery disease (CAD) is an independent risk factor for thromboembolic events including ischemic stroke in patients with atrial fibrillation (AFib), based on findings published in the Journal of the American College of Cardiology and presented at ESC Congress 2018.

Researchers examined the association between CAD and stroke in 12,690 AFib patients (18 years or above) undergoing coronary angiography between 2004-2012 in Western Denmark. Among these patients 7,533 patients (59.4 percent) had CAD and 5,157 patients (40.6 percent) did not.

The primary endpoint was a composite of ischemic stroke, transischemic attack and systemic embolism obtained from the Danish National Patient Registry. Follow-up began 30 days after the index coronary angiography and continued until endpoint event, death, emigration or end of follow-up, whichever came first. Median follow-up was three years.

The rate of the primary outcome was 2.62 per 100 person-years for patients with CAD and 1.61 per 100 person-years for patients without CAD. Researchers noted the impact of presence of CAD remained significant after adjustment and suggested a 29 percent increased risk of the primary outcome.

Their findings suggest that CAD is an independent risk factor for ischemic stroke among AFib patients. As such, they further suggest that "CAD should be considered as a potential additional risk factor in the risk scores used for stratification of AFib patients."

Steensig K, Olesen KKW, Thim T, et al. J Am Coll Cardiol 2018;Aug 26:[Epub ahead of print].

Pathological Findings in Lower-Extremity Arteries Shed Light on Progression of PAD to CLI

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Thrombotic luminal occlusion associated with insignificant atherosclerosis is commonly observed in critical limb ischemia (CLI) and suggests the possibility of thromboembolic disease, based on a study aimed at characterizing the pathology of peripheral artery disease (PAD) in below- and above-knee amputation specimens from CLI patients. The findings were presented at ESC Congress 2018 and simultaneously published in the Journal of the American College of Cardiology.

Researchers examined 299 peripheral arteries in 121 amputations specimens from 95 patients, 75 of whom presented with CLI and 20 who had amputations for other reasons. The pathological characteristics were separately recorded for femoral and popliteal arteries (FEM-POP) and infrapopliteal arteries (INFRA-POP).

Atherosclerotic plaques were more frequent in FEM-POP (23 of 34; 67.6 percent) compared with INFRA-POP (79 of 205; 38.5 percent) arteries from CLI patients. Additionally, 69 percent of the arteries from CLI patients showed ≥70 percent stenosis; in 27.3 percent this was due to significant pathological intimal thickening, fibroatheroma, fibrocalcific lesions or restenosis, luminal thrombi in 23.6 percent and in 49.1 percent there were no significant atherosclerotic lesions.

The presence of chronic luminal thrombi was more frequently observed in arteries with insignificant atherosclerosis, especially INFRA-POP. Acute thrombotic occlusion was less frequently encountered in INFRA-POP than FEM-POP arteries. Medial calcification was also present in 71.1 percent of large arteries.

"The pathological findings in lower-extremity arteries suggest possible mechanisms of progression of PAD to CLI, and may support the preventive role of antithrombotic agents," researchers said.

Narula N, Dannenberg AJ, Olin JW, et al. J Am Coll Cardiol 2018;Aug 27:[Epub ahead of print].

New Translational Research Sheds Light on Use of SGLT2 Inhibitors in Diabetes Patients

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New translational research presented at ESC Congress 2018 provides a characterization of the cardiac energetics and fuel metabolic flux in an experimental model of diabetes treated with and without the SGLT2 inhibitor empagliflozin. The study was also simultaneously published in JACC: Basic to Translational Science.

Given the growing interest in the hypothesis that SGLT2 inhibitors improve cardiac function through an effect on cardiac energy production, in part through increasing ketone body production/oxidation, researchers evaluated cardiac energy production and bioenergetics in an experimental model of diabetes treated with empagliflozin. They treated diabetic mice with or without empagliflozin and measured rates of glucose oxidation, fatty acid oxidation, ketone oxidation, glycolysis and cardiac function.

Results showed rates of glucose and ketone oxidation in the hearts of untreated diabetic mice were significantly decreased. However, fatty acid oxidation was increased with a significant overall reduction in cardiac ATP production compared with nondiabetic mice. Additionally, researchers noted that empagliflozin increased overall cardiac ATP production by roughly 30 percent and prevented cardiac failure.

Based on the findings, researchers suggest that "empagliflozin enhances the cardiac energy pool by increasing cardiac energy production from glucose and fatty acid oxidation, but not ketone oxidation." "These data provide translational clues as to how SGLT2 inhibitors may prevent cardiac failure, through augmenting glucose and fatty acid oxidation," researchers said. "Contrary to prior hypotheses, increased rates of cardiac ATP production, as opposed to increased cardiac efficiency, may explain the beneficial effects of SGLT2 inhibitors on improving cardiac function in diabetes."

In a related editorial, Peter A. Crawford, MD, PhD, writes that "ongoing experiments need to test for combinatorial effects of SGLT2 inhibition, and also account for variations posed by the model studied, including the nature of the metabolic and hemodynamic insult, as well as species- and sex-dependent differences."

Verma S, Rawat S, Ho KL, et al. JACC Basic Transl Sci 2018;Aug 26:[Epub ahead of print].

Cryoballoon Ablation For Treatment of Persistent AFib?

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Cryoballoon ablation for treatment of persistent atrial fibrillation (PerAF) had a single-procedure success rate of 61 percent at one year post ablation, based on findings presented during ESC Congress 2018 and simultaneously published in JACC: Clinical Electrophysiology.

A total of 101 patients (62 years, 74 percent male, left ventricular ejection fraction 56±8 percent, left atrial diameter 43±5 mm) were included in the multicenter single-arm study and were followed at three, six and 12 months with 48-hour Holter monitoring at six and 12 months. Quality of life and symptoms were evaluated at baseline and 12 months.

Significantly fewer patients demonstrated arrhythmia-related symptoms following cryoballoon ablation at 12 months vs. baseline (16 vs. 92 percent). Improved quality of life, in terms of physical and mental component scores, was also noted.

"The results of this study complement earlier findings and appear to suggest that a [pulmonary vein isolation]-only approach using exclusively the cryoballoon is a reasonable first line ablation strategy for the treatment of symptomatic PerAF," researchers said.

In a related editorial comment, Suneet Mittal, MD, FACC, suggests the jury is still out, noting that while "the simplicity and low complication rate are admirable and attractive" the question remains whether simplicity comes at the price of long-term success. "In the end, depending on your perspective, the glass remains either half full or half empty when it comes to using the cryoballoon in patients with persistent AFib," Mittal writes.

Boveda S, Metzner A, Nguyen DQ, et al. JACC Clin Electrophysiol 2018;Aug 25:[Epub ahead of print].

New Research Suggests Need For Better DAPT Assessment Tools

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Better tools are needed to identify patients most likely to benefit from extending dual antiplatelet therapy (DAPT) beyond 12 months following coronary stenting, said researchers presenting findings from a nationwide study showing the DAPT score did not adequately discriminate ischemic and bleeding risk. The study was presented at ESC Congress 2018 and published in the Journal of the American College of Cardiology.

Researchers followed 41,101 patients from Sweden who had undergone 12 months of event-free DAPT post stenting for an additional 18 months. They compared risk of myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (MACCE), and fatal or major bleeding using the DAPT score.

The DAPT score had a discrimination of 0.58 for MI or stent thrombosis, 0.54 for MACCE and 0.49 for fatal or major bleeding. Additionally, risk of MI or stent thrombosis was significantly greater in patients with DAPT scores of ≥3. Researchers noted MACCE risk "followed a J-shaped pattern" and increased at DAPT scores of ≥4.

Absolute differences in fatal or major bleeding risk were small between scores and event rates of ischemic outcomes were comparable. However, "fatal or major bleeding rates were approximately half of those in the placebo arm of the DAPT Study, from which the score was derived," researchers said.

Overall, the findings indicate the relationship between the score and ischemic risk do not correspond to the suggested decision rule for extended DAPT in patients with scores of ≥2. While the score may still help identify patients at high ischemic risk, researchers suggest that "the score and its decision rule may not be generalizable to real-world populations" and additional tools are needed.

"The DAPT score joins a plethora of statistical models that have uncertain utility," writes John A. Bittl, MD, FACC, in a related editorial comment. "Ueda et al., are commended for their exemplary analysis, which is a reminder that clinical decision rules must be held to a high standard. Doctors should rest assured that even the best mathematical models and prediction rules cannot replace clinical judgment."

Ueda P, Jernberg T, James S, et al. J Am Coll Cardiol 2018;Aug 26:[Epub ahead of print].

Keywords: ACC Publications, Cardiology Magazine, Adenosine Triphosphate, Amputation, Aortic Valve Stenosis, Arteries, Atherosclerosis, Atrial Fibrillation, Brain Ischemia, Benzhydryl Compounds, Constriction, Pathologic, Control Groups, Coronary Angiography, Coronary Artery Disease, Diabetes Mellitus, Experimental, Electrocardiography, Ambulatory, Electrophysiology, Embolism, Emigration and Immigration, Fatty Acids, Fibrinolytic Agents, Follow-Up Studies, Glucose, Glucosides, Glycolysis, Heart Failure, Ketones, Length of Stay, Lower Extremity, Models, Statistical, Models, Theoretical, Myocardial Infarction, Pacemaker, Artificial, Peripheral Arterial Disease, Plaque, Atherosclerotic, Popliteal Artery, Prospective Studies, Pulmonary Veins, Quality of Life, Registries, Risk Factors, Stents, Stroke, Stroke Volume, Thromboembolism, Thrombosis, Transcatheter Aortic Valve Replacement, Translational Medical Research

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