Research Spotlight

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.)

Lo, K. B., F. Gul, P. Ram, A. Y. Kluger, K. M. Tecson, P. A. McCullough and J. Rangaswami (2020). “The Effects of SGLT2 Inhibitors on Cardiovascular and Renal Outcomes in Diabetic Patients: A Systematic Review and Meta-Analysis.” Cardiorenal Med 10(1): 1-10.

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BACKGROUND: Previous meta-analyses demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) primarily on patients with established atherosclerotic cardiovascular disease (ASCVD), but with questionable efficacy on patients at risk of ASCVD. Additionally, evidence of beneficial cardiorenal outcomes in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 with the CV outcomes trials remains unclear. Canagliflozin, one of the SGLT2i, has recently been studied in a large randomized controlled trial in diabetic patients with chronic kidney disease. Thus, there is a need to understand the combined outcomes on the population targeted for treatment with SGLT2i as a whole, regardless of ASCVD status. This meta-analysis will therefore assess the efficacy of SGLT2i in cardiovascular and renal outcomes in general, and in patients with eGFR under 60 mL/min/1.73 m2 in particular. METHODS: We searched PubMed and Cochrane databases for randomized, placebo-controlled studies involving SGLT2i. We examined composite cardiovascular outcomes of death from cardiovascular causes, nonfatal myocardial infarctions, nonfatal stroke, and heart failure hospitalizations. Renal composite outcomes and progression of albuminuria were also analyzed. Pooled relative risks (RR) and their 95% confidence intervals (CI) were calculated using a fixed-effects model. RESULTS: The search yielded a total of 252 articles. Four studies were ultimately included in the meta-analysis after exclusion of other irrelevant studies. The pooled RR (95% CI) for the composite cardiovascular outcome was 0.93 (0.87-0.99) with a number needed to treat (NNT) of 167 in the general study population and 0.89 (0.77-1.02) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for all-cause mortality was 0.9 (0.84-0.97) with NNT = 143. The pooled RR for death from cardiovascular causes alone was 0.89 (0.81-0.99) in the general population and 0.82 (0.62-1.07) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for heart failure hospitalizations was 0.71 (0.63-0.79) with NNT = 91. With respect to renal outcomes, the pooled RR for the composite renal outcome was 0.63 (0.56-0.71) with NNT = 67; this was true even in patients with eGFR <60 mL/min/1.73 m2 0.67 (0.59-0.76). Lastly, the pooled RR for progression of albuminuria was 0.80 (0.76-0.84). CONCLUSION: SGLT2i are associated with significantly lower major adverse cardiovascular events, heart failure hospitalizations, and all-cause mortality. The evidence is strongest in reducing heart failure hospitalizations. However, the evidence is weaker when it comes to the population subset with eGFR <60 mL/min/1.73 m2. SGLT2i are also associated with significantly lower adverse renal events, with these effects apparent even in the population with eGFR <60 mL/min/1.73 m2.

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.

Hamandi, M., A. T. Lanfear, J. Fan, M. L. Bolin, J. M. DiMaio, R. L. Smith and C. Dib (2020). “Incidental finding of giant coronary artery aneurysm.” J Card Surg 35(1): 200-201.

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A 58‐year‐old asymptomatic man presented to our institution after a routine cardiac computed tomography (CT) for calcium scoring. He did not have any history of connective tissue disorders or Kawasaki disease. CT angiogram confirmed the presence of a coronary artery aneurysm (CAA) measuring 10.3 × 6.8 cm arising from the right coronary artery (RCA) with true lumen enhancement. The rest of the aneurysm was thrombosed, and distal calcification of the RCA was also noted. Management for patients with CAA is not standardized, as CAAs appear in only 0.3% to 5.3% of patients undergoing coronary angiographies, while “giant” CAAs (>5 cm) appear in less than 0.02%. Surgical or percutaneous intervention and antiplatelet/anticoagulation therapy are commonly reported. Due to the rarity of giant coronary aneurysms, there is no standardized management strategy supported by controlled trials. Data assessing the risk of mortality associated with these management options is sparse. The patient was referred for aneurysm ligation with distal bypass grafting due to the size and potential high risk of rupture and the risk of distal embolization which can result in myocardial ischemia or infarction. His perioperative risk of mortality and morbidity was deemed to be extremely low. Following the median sternotomy, the aneurysm was opened and the large orifice of the main right coronary artery was noted. The right coronary ostium was ligated and the old mural thrombus within the aneurysm was removed. The patient underwent coronary artery bypass grafting. The clinical course was uneventful and he was discharged on postoperative day 4. In conclusion, the management of a giant coronary artery aneurysm should be guided by the patient’s clinical presentation and perioperative risk, the size of the aneurysm, and the final decision should be made by an experienced Heart Team approach. (Excerpt from text of this image study, p. 200-201; no abstract available.)