Cardiology

Packer, M. (2019). “Risks of Intensive Treatment of Long-Standing Atrial Fibrillation in Patients With Chronic Heart Failure With a Reduced or Preserved Ejection Fraction.” Circ Cardiovasc Qual Outcomes 12(8): e005747.

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Properly designed and executed randomized controlled trials are needed to understand the appropriate strategy for rate or rhythm control for AF in patients with chronic heart failure. Such trials should focus on both patients with HFpEF and HFrEF (particularly those with an ejection fraction <30%); both phenotypes are common among patients with AF in the community. Participants would be randomized to pharmacological rate control (target rate <110/min) or to catheter ablation; because patients would have long-standing AF, they would not need cardiotoxic drugs to achieve rhythm control. Although it would be relevant to assess the effect of ablation on symptoms, quality-of-life, or exercise tolerance, these measures are readily influenced by knowledge of the treatment received. Unfortunately, sham procedures would not address the issue of blinding because patients and physicians could readily unblind the identity of their treatment by examining the pulse. However, if the trials are powered to detect a reduction in the primary end point of death, no blinding is needed. Mortality is a persuasive end point, and if the benefit of ablation on mortality is as large as is currently claimed, future trials in high-risk patients will not need to be large or follow patients for long periods of time. The proposed trial could also compare the effects of different rate targets (ventricular rate <80/min versus 90–110/min) in patients randomized to rate control and could determine if the treatment strategies yield different effects in patients with HFrEF or HFpEF . . . Until appropriate trials of rate or rhythm control are performed, physicians have little evidence to guide to the management of AF in patients with chronic heart failure. Aside from the risk of thromboembolic events, we are uncertain about the pathophysiological and clinical importance of the arrhythmia, especially in those with a long-standing arrhythmia. When intensively applied, all current therapeutic strategies—pharmacological or ablative rhythm control or drug-induced rate control—carry an important potential for harm. (Excerpts from text, p. 3-4; no abstract available.)

Packer, M. (2019). “Critical role of the epicardium in mediating cardiac inflammation and fibrosis in patients with type 2 diabetes.” Diabetes Obes Metab 21(8): 1765-1768.

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The neurohormonal imbalances that characterize diabetes may play a key role in epicardial adipogenesis, leading to the possibility that mineralocorticoid receptor antagonists and neprilysin inhibitors may be useful in reducing epicardial adipose mass, and thereby preventing or treating HFpEF, especially in patients with type 2 diabetes. Ongoing large‐scale trials are poised to test these hypotheses. In addition, imaging of epicardial adipose tissue (ideally using three‐dimensional cardiac magnetic resonance) has the potential to quantify an important source of proinflammatory cytokines in patients with type 2 diabetes, thereby identifying those at particular risk of cardiovascular or renal injury. Such patients might be particularly responsive to treatments (i.e. SGLT‐2 inhibitors) that effectively target the derangements in epicardial adipose fat depots. (Excerpt from text, p. 1766; no abstract available.)

Moayedi, Y., C. S. Fan, R. J. H. Miller, M. Tremblay-Gravel, J. G. D. Posada, C. Manlhiot, D. Hiller, J. Yee, R. Woodward, J. A. McCaughan, M. A. Shullo, S. A. Hall, S. Pinney, K. K. Khush, H. J. Ross and J. J. Teuteberg (2019). “Gene expression profiling and racial disparities in outcomes after heart transplantation.” J Heart Lung Transplant 38(8): 820-829.

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BACKGROUND: African Americans (AAs) have lower survival rates after heart transplantation (HTx) than Caucasians. The aim of this analysis was to evaluate racial differences in gene expression and their associations with survival and the composite outcome of death, retransplant, rejection with hemodynamic compromise, and graft dysfunction in the Outcomes AlloMap Registry. METHODS: Registry participants included low-risk Caucasian and AA heart transplant recipients with a baseline and at least 1 follow-up gene expression test (AlloMap(C)) within the first year after HTx. The Kaplan-Meier method with delayed entry was used to describe differences in outcomes. Multivariable Cox hazard regression was used to evaluate the associations of overall gene expression profiling score, MARCH8 and FLT3 expression, and tacrolimus levels with each outcome, and stratified Cox models were developed to quantify race-specific associations. RESULTS: Among 933 eligible recipients, 737 (79%) were Caucasian and 196 (21%) were AA. Compared with Caucasians, AAs were significantly younger (55 vs 59 years, p < 0.001), with higher rates of non-ischemic cardiomyopathy (68% vs 50%, p < 0.001), sensitization (>10% panel reactive antibody, 16% vs 9.1%, p=0.009), and human leukocyte antigen mismatches (7 vs 7, p=0.01), but less frequent primary cytomegalovirus serostatus mismatch (14.31% vs 27.3%, p < 0.001). Overall, AAs had an increased adjusted mortality risk (hazard ratio [HR] 4.13, p=0.007). Higher tacrolimus levels were associated with decreased mortality in AAs (HR 0.62, p=0.009). Overall gene expression profiling score was associated with increased mortality among Caucasians (HR 1.21, p=0.048). In Caucasians, but not AAs, overexpression of MARCH8 was associated with increased mortality (HR 2.90, p=0.001). FLT3 upregulation was associated with increased mortality (HR 2.42, p=0.033) in AAs. There was an inverse relationship between FLT3 expression and tacrolimus levels (-0.029 and -0.176, respectively) in Caucasians and AAs. CONCLUSIONS: AAs have a significantly higher mortality risk after HTx than Caucasians, even in the low-risk Outcomes AlloMap Registry population. AAs and Caucasians had differential outcomes based upon the varying expression of MARCH8 and FLT3 genes following HTx.

Lim, D. S., S. Kar, K. Spargias, R. M. Kipperman, W. W. O’Neill, M. K. C. Ng, N. P. Fam, D. L. Walters, J. G. Webb, R. L. Smith, M. J. Rinaldi, A. Latib, G. N. Cohen, U. Schafer, L. Marcoff, P. Vandrangi, P. Verta and T. E. Feldman (2019). “Transcatheter Valve Repair for Patients With Mitral Regurgitation: 30-Day Results of the CLASP Study.” JACC Cardiovasc Interv 12(14): 1369-1378.

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OBJECTIVES: The authors report the procedural and 30-day results of the PASCAL Transcatheter Valve Repair System (Edwards Lifesciences, Irvine, California) in patients with mitral regurgitation (MR) enrolled in the multicenter, prospective, single-arm CLASP study. BACKGROUND: Severe MR may lead to symptoms, impaired quality of life, and reduced functional capacity when untreated. METHODS: Eligible patients had grade 3+ or 4+ MR despite optimal medical therapy and were deemed appropriate for the study by the local heart team. All outcomes were assessed through 30 days post-procedure. Major adverse events (MAEs) were adjudicated by an independent clinical events committee, and echocardiographic images were assessed by a core laboratory. The primary safety endpoint was the rate of MAEs at 30 days. RESULTS: Between June 2017 and September 2018, 62 patients with grade 3+ or 4+ MR were enrolled. The mean age was 76.5 years, and 51.6% of patients were in New York Heart Association functional class III or IV, with 56% functional, 36% degenerative, and 8% mixed MR etiology. At 30 days, the MAE rate was 6.5%, with an all-cause mortality rate of 1.6% and no occurrence of stroke; 98% had MR grade

Edgerton, J. R. (2019). “Invited Commentary.” Ann Thorac Surg 108(2): 450-451.

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In this issue of The Annals of Thoracic Surgery, the Washington University group reports the results of surgical ablation of atrial fibrillation (AF) in 34 patients with tachycardia-induced cardiomyopathy (TIC) defined as left ventricular ejection fraction less than 41% and absent another etiology. Excluding 1 death, 33 patients were available for follow-up, and 27 of these patients had an evaluable echocardiogram at approximately 12 months. At 12 months, 94% of patients were free of atrial tachyarrhythmias with or without antiarrhythmic drugs. Mean left ventricular ejection fraction improved from 32% to 55%. Of 11 patients in New York Hearth Association Class III/IV, 8 patients improved to Class I/II. These changes reached statistical significance. It is important to note that LV function improved in all patients, and it improved to greater than 55% in 19 of 27 patients. The prognostic significance of the presence of fibrosis (inhibits recovery of function), as reported in the CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction) study and reiterated in this report, should be stressed. In patient selection, it is important to differentiate between TIC and a dilated cardiomyopathy with secondary AF. The patient with TIC is likely to be helped by performing a Maze whereas the patient with a dilated cardiomyopathy secondary to AF is not. To differentiate, the authors perform a cardiac magnetic resonance imaging (MRI) to assess for myocardial viability and the degree of left ventricular fibrosis by late gadolinium enhancement. On multivariate analysis, only the absence of late gadolinium enhancement was found to predict left ventricular ejection fraction normalization. Any presence of fibrosis rules the patient out as a candidate for surgical ablation. If there is any other abnormality on cardiac MRI, or a high index of suspicion, endomyocardial biopsies are performed. Thus, preoperative MRI will help the clinician in deciding whether to operate for TIC. Although the numbers of patients are small, documenting these findings is significant. It would be easy for a reader to dismiss this article as a small retrospective series of little significance. This would be a grave error. Yes, the numbers are small, but few groups have adequate volume to accumulate this many patients, and most lack the investigatory rigor to document the postoperative course in such detail. In addition, few groups have preoperative MRI for these patients. As the authors point out, current guideline statements on the treatment of TIC, “include only non-surgical rhythm control strategies.” This is the true significance of this article. Considering the findings documented here, a Class IIa, Level of Evidence B-NR is justified for surgical ablation of AF in patients with TIC who are undergoing cardiac surgery for another reason or who have failed antiarrhythmic drugs and catheter ablation. Future guideline committees need to consider this work when revising current guidelines. (Full text of this commentary.)