Cardiology

Meduri, C. U., M. J. Reardon, D. Scott 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 Oct 11. [Epub ahead of print].

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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.

Meduri, C. U., D. J. Kereiakes, V. Rajagopal, R. R. Makkar, D. O’Hair, A. Linke, R. Waksman, V. Babliaros, R. C. Stoler, G. J. Mishkel, D. G. Rizik, V. S. Iyer, J. Schindler, D. J. Allocco, I. T. Meredith, T. E. Feldman and M. J. Reardon (2019). “Pacemaker Implantation and Dependency After Transcatheter Aortic Valve Replacement in the REPRISE III Trial.” J Am Heart Assoc Nov 5: 8(21). [Epub 2019 Oct 23].

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Background As transcatheter aortic valve replacement expands to younger and/or lower risk patients, the long-term consequences of permanent pacemaker implantation are a concern. Pacemaker dependency and impact have not been methodically assessed in transcatheter aortic valve replacement trials. We report the incidence and predictors of pacemaker implantation and pacemaker dependency after transcatheter aortic valve replacement with the Lotus valve. Methods and Results A total of 912 patients with high/extreme surgical risk and symptomatic aortic stenosis were randomized 2:1 (Lotus:CoreValve) in REPRISE III (The Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System-Randomized Clinical Evaluation) trial. Systematic assessment of pacemaker dependency was pre-specified in the trial design. Pacemaker implantation within 30 days was more frequent with Lotus than CoreValve. By multivariable analysis, predictors of pacemaker implantation included baseline right bundle branch block and depth of implantation; diabetes mellitus was also a predictor with Lotus. No association between new pacemaker implantation and clinical outcomes was found. Pacemaker dependency was dynamic (30 days: 43%; 1 year: 50%) and not consistent for individual patients over time. Predictors of pacemaker dependency at 30 days included baseline right bundle branch block, female sex, and depth of implantation. No differences in mortality or stroke were found between patients who were pacemaker dependent or not at 30 days. Rehospitalization was higher in patients who were not pacemaker dependent versus patients without a pacemaker or those who were dependent. Conclusions Pacemaker implantation was not associated with adverse clinical outcomes. Most patients with a new pacemaker at 30 days were not dependent at 1 year. Mortality and stroke were similar between patients with or without pacemaker dependency and patients without a pacemaker. Clinical Trial Registration Unique identifier NCT02202434.

McCullough, P. A., H. S. Mehta, C. M. Barker, D. P. Cork, C. Gunnarsson, M. P. Ryan, E. R. Baker, J. Van Houten, S. Mollenkopf and P. Verta (2019). “The Economic Impact of Mitral Regurgitation on Patients With Medically Managed Heart Failure.” Am J Cardiol 124(8): 1226-1231.

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The objective of this study was to quantify the financial healthcare burden of mitral regurgitation (MR) on medically managed heart failure (HF) patients. Data from the Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases were analyzed. Included patients had a minimum of 1 inpatient or 2 outpatient claims for HF with a 6-month preperiod (baseline). A 6-month postperiod (landmark) after HF index was used to capture MR diagnosis and severity. Following the landmark period, patients had to have 12 months of continuous medical and prescription drug plan enrollment with at least 2 records of HF medication refills. A therapeutic intensity score was calculated based on HF medication usage. Medically managed HF patients were separated into 3 cohorts: without MR (no MR), insignificant MR (iMR), and significant MR (sMR). Healthcare utilization and all-cause expenditures were modeled to quantify the burden of MR. All models controlled for baseline demographics, co-morbid conditions, and HF therapeutic intensity. Medically managed incident HF patients with sMR had significantly more hospital days (1.91 vs 1.72 days; p=0.0096) and annual expenditures ($23,988 vs $21,530; p < 0.0001) compared with no MR patients. No differences were identified when comparing iMR and no MR. When evaluating HF admissions, sMR patients had an estimated 50% greater HF admissions rate (0.036 vs 0.024; p < 0.0001) compared with no MR patients. Additionally, HF admits for iMR were 23% more than those with no MR (0.029 vs 0.024; p=0.0064). In conclusion, evidence of MR in retrospective claims significantly increases the healthcare impact of medically managed HF patients. Both utilization and financial burden is more pronounced when MR is clinically significant.

Husain-Syed, F., H. W. Birk, C. Ronco, T. Schormann, K. Tello, M. J. Richter, J. Wilhelm, N. Sommer, E. Steyerberg, P. Bauer, H. D. Walmrath, W. Seeger, P. A. McCullough, H. Gall and H. A. Ghofrani (2019). “Doppler-Derived Renal Venous Stasis Index in the Prognosis of Right Heart Failure.” J Am Heart Assoc Nov 5;8(21). [Epub 2019 Oct 19].

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Background Persistent congestion with deteriorating renal function is an important cause of adverse outcomes in heart failure. We aimed to characterize new approaches to evaluate renal congestion using Doppler ultrasonography. Methods and Results We enrolled 205 patients with suspected or prediagnosed pulmonary hypertension (PH) undergoing right heart catheterization. Patients underwent renal Doppler ultrasonography and assessment of invasive cardiopulmonary hemodynamics, echocardiography, renal function, intra-abdominal pressure, and neurohormones and hydration status. Four spectral Doppler intrarenal venous flow patterns and a novel renal venous stasis index (RVSI) were defined. We evaluated PH-related morbidity using the Cox proportional hazards model for the composite end point of PH progression (hospitalization for worsening PH, lung transplantation, or PH-specific therapy escalation) and all-cause mortality for 1-year after discharge. The prognostic utility of RVSI and intrarenal venous flow patterns was compared using receiver operating characteristic curves. RVSI increased in a graded fashion across increasing severity of intrarenal venous flow patterns (P<0.0001) and was significantly associated with right heart and renal function, intra-abdominal pressure, and neurohormonal and hydration status. During follow-up, the morbidity/mortality end point occurred in 91 patients and was independently predicted by RVSI (RVSI in the third tertile versus referent: hazard ratio: 4.72 [95% CI, 2.10-10.59; P<0.0001]). Receiver operating characteristic curves suggested superiority of RVSI to individual intrarenal venous flow patterns in predicting outcome (areas under the curve: 0.789 and 0.761, respectively; P=0.038). Conclusions We propose RVSI as a conceptually new and integrative Doppler index of renal congestion. RVSI provides additional prognostic information to stratify PH for the propensity to develop right heart failure. Clinical Trial Registration Unique identifier: NCT03039959.

Vemulapalli, S., J. D. Carroll and M. J. Mack (2019). “Volume and Outcomes for Transcatheter Aortic-Valve Replacement. Reply.” New England Journal of Medicine 381(14): 1394-1395.

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We agree with Noble and Frei that 30-day mortality should not be the sole indicator of site quality. We are currently deriving and validating metrics that emphasize a composite of 30-day morbidity and mortality as well as “alive and well” status at 1 year on the basis of survival and improved quality of life. Yet, the measurement of 30-day mortality remains vital for patient safety. Our analyses of volume suggest that it is a surrogate for quality and that adequate volume is necessary to accurately estimate expected risk-adjusted outcomes. Goldberg et al. raise the complex issue of geographic access to TAVR, for which there are few data. In the United States, we have a “spoke and hub” medical system with centralization of some services because of cost, infrastructure, and quality considerations. As a result, TAVR is not unique in being restricted to certain centers. Despite this, the United States has more hospitals, and more hospitals per capita, performing TAVR than any other country. Although geography is relatively easily measured, access to care is a complex construct of geographic location, socioeconomic status, ethnic group, race, insurance status, patients’ preferences, and physician-related factors, among others. More research is needed to clarify the extent to which each of these factors contributes to access to care issues for TAVR. Our analysis did not fully address access to TAVR, and the analysis that Goldberg and Gray suggested may lead to interesting results. We agree with Sharma that the results of our study were relevant to the CMS National Coverage Determination. However, we differ with Sharma’s interpretation of our results and their relationship to the findings of Russo et al. Russo and colleagues examined only one commercially approved device, defined the beginning of the learning curve on the basis of the first use of the latest generation of the SAPIEN system rather than on the basis of all previous experience, and probably underestimated the site volume by not including CoreValve use. We constructed hierarchical models that accounted for operator case number and then modeled the marginal effect of annual volume on mortality beyond the contribution of operator case number. Since the “learning curve” is essentially defined by mortality as a function of case number, modeling the association between volume and mortality after taking into account case number effectively isolates the annual volume–mortality relationship from the learning curve. With this technique, we found that there was a volume–mortality relationship beyond the learning curve and that it was independent of procedure year and patient risk. (Authors’ reply to correspondence about their article, Vemulapalli S, Carroll JD, Mack MJ, et al. Procedural volume and outcomes for transcatheter aortic-valve replacement. N Engl J Med 2019;380:2541-2550.)