Research Spotlight

Piffaretti, G., V. Grassi, C. Lomazzi, W. T. Brinkman, T. P. Navarro, M. P. Jenkins and S. Trimarchi (2019). “Thoracic endovascular stent graft repair for ascending aortic diseases.” J Vasc Surg 70(5): 1384-1389.e1381.

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OBJECTIVES: We describe the preliminary results of thoracic endovascular aortic repair (TEVAR) in a group of patients with ascending aortic disease from the Global Registry for Endovascular Aortic Treatment (GREAT). METHODS: We identified TEVAR performed for diseases truly originating from the ascending aorta. Between July 2011 and May 2015, 5014 patients were enrolled; six (0.12%) were identified and included in the analysis. One further patient was withdrawn from the study due to lack of a signed consent form. Patients having a “zone 0” proximal landing zone reported for their TEVAR without the presence of an ascending aortic disease were not included. Reinterventions of previous open and endovascular repair were also excluded. RESULTS: Three males and three females were treated. Mean age was 69 years +/- 10 years (range, 58-83 years). Indication for TEVAR was atherosclerotic aneurysm (n = 4; ruptured, n = 1), complicated type A dissection (n = 1, rupture), and pseudoaneurysm (n = 1). Mean maximum aortic lesion diameter was 60 mm 14 (range, 39-77 mm). Urgent intervention was performed in three (50%) cases. Primary clinical success was 100%. There was no TEVAR-related in-hospital mortality. Open conversion was never required. Complication such as cerebrovascular accidents, valve impairment, or myocardial infarction did not occur. All patients were discharged home alive. No patient was lost at a median follow-up of 26 months (range, 16-72 months). During the follow-up, no patient died and ongoing primary clinical success was maintained in all patients. Reintervention was never required; endoleaks, migrations, fractures, or ruptures were not observed. CONCLUSIONS: Preliminary “real-world” experience of ascending TEVAR shows satisfactory outcomes at short-term follow-up. Although concerns remain for “off-label” use of standard devices, TEVAR-related complications were not observed. Longer follow-up data are expected to confirm durability of these results.

Packer, M. (2019). “Methodological and Clinical Heterogeneity and Extraction Errors in Meta-Analyses of Catheter Ablation for Atrial Fibrillation in Heart Failure.” J Am Heart Assoc Nov 5: 8(21). [Epub 2019 Oct 18].

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Background Meta-analyses are expected to follow a standardized process, and thus, they have become highly formulaic, although there is little evidence that such regimentation yields high-quality results. Methods and Results This article describes the results of a critical examination of 14 published meta-analyses of catheter ablation for atrial fibrillation in heart failure that were based on a nearly identical core set of 4 to 6 primary trials. Methodological issues included (1) the neglect of primary data or the failure to report any primary data; (2) the inaccurate recording of the number of randomized patients; (3) the lack of attention to data missingness or baseline imbalances; (4) the failure to contact investigators of primary trials for additional data; (5) the incorrect extraction of data, the misidentification of events, and the assignment of events to the wrong treatment groups; (6) the calculation of summary estimates based on demonstrably heterogenous data, methods of differing reliability, or unrelated end points; and (7) the development of conclusions based on sparse numbers of events or overly reliant on the results of 1 dominant trial. Conclusions These findings reinforce existing concerns about the methodological validity of meta-analyses and their current status in the hierarchy of medical evidence, and they raise new questions about the process by which meta-analyses undergo peer review by medical journals.

Packer, M. (2019). “Methodological and Clinical Heterogeneity and Extraction Errors in Meta-Analyses of Catheter Ablation for Atrial Fibrillation in Heart Failure.” J Am Heart Assoc Nov 5: 8(21). [Epub 2019 Oct 18].

Full text of this article.

Background Meta-analyses are expected to follow a standardized process, and thus, they have become highly formulaic, although there is little evidence that such regimentation yields high-quality results. Methods and Results This article describes the results of a critical examination of 14 published meta-analyses of catheter ablation for atrial fibrillation in heart failure that were based on a nearly identical core set of 4 to 6 primary trials. Methodological issues included (1) the neglect of primary data or the failure to report any primary data; (2) the inaccurate recording of the number of randomized patients; (3) the lack of attention to data missingness or baseline imbalances; (4) the failure to contact investigators of primary trials for additional data; (5) the incorrect extraction of data, the misidentification of events, and the assignment of events to the wrong treatment groups; (6) the calculation of summary estimates based on demonstrably heterogenous data, methods of differing reliability, or unrelated end points; and (7) the development of conclusions based on sparse numbers of events or overly reliant on the results of 1 dominant trial. Conclusions These findings reinforce existing concerns about the methodological validity of meta-analyses and their current status in the hierarchy of medical evidence, and they raise new questions about the process by which meta-analyses undergo peer review by medical journals.

Packer, M. (2019). “Heightened risk of intensive rate control in patients with atrial fibrillation who are obese or have type 2 diabetes: A critical review and re-evaluation.” J Cardiovasc Electrophysiol Oct 18. [Epub ahead of print].

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Atrial fibrillation (AF) is common in patients with obesity and diabetes; the arrhythmia (if long-standing) is typically managed by rate control and anticoagulation. However, the coexistence of these two metabolic disorders complicates therapeutic options for rate control. The likely pathogenesis of AF in these patients is an expansion of epicardial adipose tissue whose inflammation is transmitted to the left atrium causing electromechanical remodeling. However, this same process is also transmitted to the left ventricle (LV), impairing its distensibility and its ability to tolerate volume, leading to heart failure with preserved ejection fraction. Unfortunately, the latter diagnosis (although commonly present in patients with AF and a coexistent metabolic disorder) is often ignored. To achieve rate control, physicians prescribe intensive treatment with atrioventricular (AV) nodal-blocking drugs, often at doses that are titrated to blunt exercise as well as resting heart rate responses. However, strict rate control (target rate, <80/min) is associated with somewhat worse outcomes than lenient rate control (target rate, <110/min). Furthermore, any rate slowing that facilitates diastolic filling may aggravate filling pressures that are already disproportionately increased because the LV is stiff and overfilled as a result of cardiac inflammation. Rate slowing in AF with beta blockers may not achieve the benefit expected from the blockade of adrenergically mediated cardiotoxicity, and some AV nodal-blocking drugs (digoxin and dronedarone) can increase the risk of death in patients with AF. Finally, cardiac fibrosis in obesity and diabetes may affect the conduction system, which can predispose to serious bradyarrhythmias if patients are prescribed AV nodal-blocking drugs.

Packer, M. (2019). “Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction in Patients With Nonalcoholic Fatty Liver Disease.” Am J Med Oct 14. [Epub ahead of print].

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The most common causes of chronic liver disease in the developed world -nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) – are the hepatic manifestations of an insulin-resistant state that is linked to visceral adiposity and systemic inflammation. NAFLD and NASH lead to an expansion of epicardial adipose tissue and the release of proinflammatory adipocytokines that cause microcirculatory dysfunction and fibrosis of the adjoining myocardium, resulting in atrial fibrillation as well as heart failure with a preserved ejection fraction (HFpEF). Inflammatory changes in the left atrium lead to electroanatomical remodeling; thus, NAFLD and NASH markedly increase the risk of atrial fibrillation. Simultaneously, patients with NAFLD or NASH commonly show diastolic dysfunction or latent HFpEF. Interventions include (1) weight loss by caloric restriction, bariatric surgery or intensive exercise; and (2) drugs that ameliorate fat-mediated inflammation in both the liver and heart (e.g., statins, metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and pioglitazone). Patients with NAFLD or NASH commonly have an inflammation-related atrial and ventricular myopathy, which may contribute to symptoms and long-term outcomes.