Cardiology

Packer, M. (2020). “Do amiodarone and dronedarone prevent thrombo-embolic stroke by treating the atrial myopathy of patients with atrial fibrillation? A provocative hypothesis.” Europace Jan 3. [Epub ahead of print].

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Aside from the relief of arrhythmia-related symptoms, the major reason to treat AF is to prevent the occurrence of systemic thromboembolism, since there remains uncertainty as to the role of AF in the progression of cardiomyopathy or heart failure. There is a growing interest in the use of catheter ablation as a first-line treatment for AF, since it is generally more effective than drug therapy in abolishing the arrhythmia, and it often spares patients from receiving potentially toxic antiarrhythmic agents. However, any preference for catheter ablation should be tempered by the possibility that certain Class III antiarrhythmic drugs may have an effect to reduce the risk of stroke because of a direct benefit on the underlying atrial myopathy. Oral anticoagulation is the most important treatment for the prevention of stroke, but many patients with AF are not prescribed these drugs or remain at risk of stroke despite receiving long-term anticoagulation. Additionally, because it exacerbates the underlying atrial myopathy, AF ablation without concomitant Class III antiarrhythmic drugs may not provide optimal protection against stroke, even in those who are prescribed oral anticoagulants. Therefore, in patients with AF who are at meaningful risk of stroke, physicians may well be advised to assess the presence and severity of an underlying atrial myopathy as a means of guiding their treatment decisions. (Excerpt from text, p. 2-3; no abstract available.)

Packer, M. (2019). “Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment.” Eur J Heart Fail Dec 17. [Epub ahead of print].

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Obesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial pressures at rest or during exercise, even in the absence of diagnosed HFpEF. Among patients with AF, those who also have latent HFpEF have increased risk for systemic thromboembolism and death. The identification of HFpEF in patients with obesity or diabetes alters the risk-to-benefit relationship of commonly prescribed treatments. Bariatric surgery and statins can ameliorate AF and reduce the risk for HFpEF. Conversely, antihyperglycaemic drugs that promote adipogenesis or cause sodium retention (insulin and thiazolidinediones) may increase the risk for heart failure in patients with an underlying ventricular myopathy. Patients with obesity and diabetes who undergo catheter ablation for AF are at increased risk for AF recurrence and for post-ablation increases in pulmonary venous pressures and worsening heart failure, especially if HFpEF coexists. Therefore, AF may be the earliest indicator of HFpEF in patients with obesity or type 2 diabetes, and recognition of HFpEF alters the management of these patients.

Meduri, C. U., M. J. Reardon, D. S. Lim, E. Howard, G. Dunnington, D. P. Lee, D. Liang, R. Gooley, D. O’Hair, M. K. Ng, A. Walton, K. Spargias, D. Blackman, A. Coisne, D. Hildick-Smith, M. De Gouy, S. Chenoweth, S. Kar, P. M. McCarthy, N. Piazza, A. Qasam, R. P. Martin, M. B. Leon, M. J. Mack, D. H. Adams and V. Bapat (2019). “Novel Multiphase Assessment for Predicting Left Ventricular Outflow Tract Obstruction Before Transcatheter Mitral Valve Replacement.” JACC Cardiovasc Interv 12(23): 2402-2412.

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OBJECTIVES: This study proposes a physiologic assessment of left ventricular outflow tract obstruction (LVOTO) that accommodates changes in systolic flow and accounts for the dynamic neo-left ventricular outflow tract (LVOT). BACKGROUND: Patients considered for transcatheter mitral valve replacement trials often screen-fail because of the perceived risk of LVOTO. In the Intrepid Global Pilot Study, assumed risk of LVOTO was based on computed tomography estimates of the neo-LVOT area computed at end-systole. However, this may overestimate actual risk. METHODS: Retrospective analyses were performed for screen-failed patients for potential LVOTO (n = 33) and treated patients (n = 29) with available dynamic computed tomography. A multiphase assessment of the neo-LVOT area was performed and represented as: 1) multiphase average; and 2) early systolic value. Prospective evaluation was performed in 9 patients approved for enrollment with multiphase and early systole methods that would have previously screen-failed with the end-systolic approach. RESULTS: Of 166 patients screened for possible inclusion; 32 were screen-failed for nonanatomical reasons. Screen failure for assumed LVOTO risk occurred in 37 of 134 (27.6%) patients. Retrospective analysis indicated a potential enrollment increase of 11 of 33 (33.3%) and 18 of 33 (54.5%) patients using multiphase and early systolic assessment methods. In the prospective cohort, there were no clinical observations of LVOTO 30 days post-procedure, despite assumed risk based on end-systolic estimates. CONCLUSIONS: Multiphase, and specifically early systolic, assessment of the neo-LVOT may better determine risk of LVOTO with transcatheter mitral valve replacement compared with end-systolic estimates. This novel approach has the potential to significantly increase patient eligibility, with over one-half of patients previously screen-failed now eligible for treatment.

Mack, M. and P. Grayburn (2019). “A tale of two trials; chapter 2.” Eur J Heart Fail 21(12): 1635-1637.

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Last year witnessed the simultaneous publication of two randomized trials attempting to determine the benefits (if any) of the correction of moderate to severe or severe secondary (functional) mitral regurgitation (MR) with the MitraClip device (Abbott Inc, Santa Clara, CA, USA) in addition to guideline‐directed medical therapy (GDMT) in patients with heart failure (HF). One trial, the COAPT trial, was unequivocally positive demonstrating clear benefit in the primary effectiveness endpoint of all HF hospitalizations within 24 months.1 Also demonstrated in this trial was a mortality benefit and the trial met all 10 of the pre‐specified and powered secondary endpoints. However, the other trial, MITRA‐FR, conducted in approximately the same time frame in a similar study cohort of patients, found a diametrically opposite result with no demonstrable benefit in the primary effectiveness endpoint of death and HF hospitalization at 12 months.2 These discordant outcomes obtained using the same device to treat the same disease at roughly the same time has led to much debate and conjecture as how to explain these seemingly irreconcilable differences. (Excerpt from text of this commentary on “Percutaneous repair or medical treatment for secondary mitral regurgitation: outcomes at 2 years’’ by B. Iung et al., published in the same issue.)

Kotecha, D., S. K. Gill, M. D. Flather, J. Holmes, M. Packer, G. Rosano, M. Bohm, J. J. V. McMurray, J. Wikstrand, S. D. Anker, D. J. van Veldhuisen, L. Manzano, T. G. von Lueder, A. S. Rigby, B. Andersson, J. Kjekshus, H. Wedel, F. Ruschitzka, J. G. F. Cleland, K. Damman, J. Redon and A. J. S. Coats (2019). “Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.” J Am Coll Cardiol 74(23): 2893-2904.

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BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m(2); 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m(2), and 2,286 (13.7%) 30 to 44 ml/min/1.73 m(2). Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m(2) lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m(2) (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m(2) (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m(2)) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.