Emerging Evidence on Coronary Heart Disease Screening in Kidney and Liver Transplantation Candidates: A Scientific Statement From the American Heart Association: Endorsed by the American Society of Transplantation.

Coronary heart disease is an important source of mortality and morbidity among kidney transplantation and liver transplantation candidates and recipients and is driven by traditional and nontraditional risk factors related to end-stage organ disease. In this scientific statement, we review evidence from the past decade related to coronary heart disease screening and management for kidney and liver transplantation candidates. Coronary heart disease screening in asymptomatic kidney and liver transplantation candidates has not been demonstrated to improve outcomes but is common in practice. Risk stratification algorithms based on the presence or absence of clinical risk factors and physical performance have been proposed, but a high proportion of candidates still meet criteria for screening tests. We suggest new approaches to pretransplantation evaluation grounded on the presence or absence of known coronary heart disease and cardiac symptoms and emphasize multidisciplinary engagement, including involvement of a dedicated cardiologist. Noninvasive functional screening methods such as stress echocardiography and myocardial perfusion scintigraphy have limited accuracy, and newer noninvasive modalities, especially cardiac computed tomography-based tests, are promising alternatives. Emerging evidence such as results of the 2020 International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease trial emphasizes the vital importance of guideline-directed medical therapy in managing diagnosed coronary heart disease and further questions the value of revascularization among asymptomatic kidney transplantation candidates. Optimizing strategies to disseminate and implement best practices for medical management in the broader end-stage organ disease population should be prioritized to improve cardiovascular outcomes in these populations.

Lateral annular systolic excursion ratio: A novel measurement of right ventricular systolic function by two-dimensional echocardiography.

Introduction: Accurate assessment of right ventricular (RV) systolic function has prognostic and therapeutic implications in many disease states. Echocardiography remains the most frequently deployed imaging modality for this purpose, but estimation of RV systolic function remains challenging. The purpose of this study was to evaluate the diagnostic performance of a novel measurement of RV systolic function called lateral annular systolic excursion ratio (LASER), which is the fractional shortening of the lateral tricuspid annulus to apex distance, compared to right ventricular ejection fraction (RVEF) derived by cardiac magnetic resonance imaging (CMR). Methods: A retrospective cohort of 78 consecutive patients who underwent clinically indicated CMR and transthoracic echocardiography within 30 days were identified from a database. Parameters of RV function measured included: tricuspid annular plane systolic excursion (TAPSE) by M-mode, tissue Doppler S', fractional area change (FAC) and LASER. These measurements were compared to RVEF derived by CMR using Pearson's correlation coefficients and receiver operating characteristic curves. Results: LASER was measurable in 75 (96%) of patients within the cohort. Right ventricular systolic dysfunction, by CMR measurement, was present in 37% (n = 29) of the population. LASER has moderate positive correlation with RVEF (r = 0.54) which was similar to FAC (r = 0.56), S' (r = 0.49) and TAPSE (r = 0.37). Receiver operating characteristic curves demonstrated that LASER (AUC = 0.865) outperformed fractional area change (AUC = 0.767), tissue Doppler S' (AUC = 0.744) and TAPSE (AUC = 0.645). A cohort derived dichotomous cutoff of 0.2 for LASER was shown to provide optimal diagnostic characteristics (sensitivity of 75%, specificity of 87% and accuracy of 83%) for identifying abnormal RV function. LASER had the highest sensitivity, accuracy, positive and negative predictive values among the parameters studied in the cohort. Conclusions: Within the study cohort, LASER was shown to have moderate positive correlation with RVEF derived by CMR and more favorable diagnostic performance for detecting RV systolic dysfunction compared to conventional echocardiographic parameters while being simple to obtain and less dependent on image quality than FAC and emerging techniques.

Incidence, Clinical Correlates, and Outcomes of Pulmonary Hypertension After Kidney Transplantation: Analysis of Linked US Registry and Medicare Billing Claims.

BACKGROUND: The incidence, risks, and outcomes associated with pulmonary hypertension (P-HTN) in the kidney transplant (KTx) population are not well described. METHODS: We linked US transplant registry data with Medicare claims (2006-2016) to investigate P-HTN diagnoses among Medicare-insured KTx recipients (N = 35 512) using billing claims. Cox regression was applied to identify independent correlates and outcomes of P-HTN (adjusted hazard ratio [aHR] 95%LCLaHR95%UCL) and to examine P-HTN diagnoses as time-dependent mortality predictors. RESULTS: Overall, 8.2% of recipients had a diagnostic code for P-HTN within 2 y preceding transplant. By 3 y posttransplant, P-HTN was diagnosed in 10.310.6%11.0 of the study cohort. After adjustment, posttransplant P-HTN was more likely in KTx recipients who were older (age ≥60 versus 18-30 y a HR, 1.912.403.01) or female (aHR, 1.151.241.34), who had pretransplant P-HTN (aHR, 4.384.795.24), coronary artery disease (aHR, 1.051.151.27), valvular heart disease (aHR, 1.221.321.43), peripheral vascular disease (aHR, 1.051.181.33), chronic pulmonary disease (aHR, 1.201.311.43), obstructive sleep apnea (aHR, 1.151.281.43), longer dialysis duration, pretransplant hemodialysis (aHR, 1.171.371.59), or who underwent transplant in the more recent era (2012-2016 versus 2006-2011: aHR, 1.291.391.51). Posttransplant P-HTN was associated with >2.5-fold increased risk of mortality (aHR, 2.572.843.14) and all-cause graft failure (aHR, 2.422.642.88) within 3 y posttransplant. Outcome associations of newly diagnosed posttransplant P-HTN were similar. CONCLUSIONS: Posttransplant P-HTN is diagnosed in 1 in 10 KTx recipients and is associated with an increased risk of death and graft failure. Future research is needed to refine diagnostic, classification, and management strategies to improve outcomes in KTx recipients who develop P-HTN.

Kidney Transplant List Status and Outcomes in the ISCHEMIA-CKD Trial.

BACKGROUND: Patients with chronic kidney disease (CKD) and coronary artery disease frequently undergo preemptive revascularization before kidney transplant listing. OBJECTIVES: In this post hoc analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness of Medical and Invasive Approaches-Chronic Kidney Disease), we compared outcomes of patients not listed versus those listed according to management strategy. METHODS: In the ISCHEMIA-CKD trial (n = 777), 194 patients (25%) with chronic coronary syndromes and at least moderate ischemia were listed for transplant. The primary (all-cause mortality or nonfatal myocardial infarction) and secondary (death, nonfatal myocardial infarction, hospitalization for unstable angina, heart failure, resuscitated cardiac arrest, or stroke) outcomes were analyzed using Cox multivariable modeling. Heterogeneity of randomized treatment effect between listed versus not listed groups was assessed. RESULTS: Compared with those not listed, listed patients were younger (60 years vs 65 years), were less likely to be of Asian race (15% vs 29%), were more likely to be on dialysis (83% vs 44%), had fewer anginal symptoms, and were more likely to have coronary angiography and coronary revascularization irrespective of treatment assignment. Among patients assigned to an invasive strategy versus conservative strategy, the adjusted hazard ratios for the primary outcome were 0.91 (95% confidence interval [CI]: 0.54-1.54) and 1.03 (95% CI: 0.78-1.37) for those listed and not listed, respectively (pinteraction= 0.68). Adjusted hazard ratios for secondary outcomes were 0.89 (95% CI: 0.55-1.46) in listed and 1.17 (95% CI: 0.89-1.53) in those not listed (pinteraction = 0.35). CONCLUSIONS: In ISCHEMIA-CKD, an invasive strategy in kidney transplant candidates did not improve outcomes compared with conservative management. These data do not support routine coronary angiography or revascularization in patients with advanced CKD and chronic coronary syndromes listed for transplant. (ISCHEMIA-Chronic Kidney Disease Trial [ISCHEMIA-CKD]; NCT01985360).

Concepts and Controversies: Lipid Management in Patients with Chronic Kidney Disease.

Atherosclerotic cardiovascular disease (ASCVD) remains an important contributor of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is recognized as an important risk enhancer that identifies patients as candidates for more intensive low-density lipoprotein (LDL) cholesterol lowering. However, there is controversy regarding the efficacy of lipid-lowering therapy, especially in patients on dialysis. Among patients with CKD, not yet on dialysis, there is clinical trial evidence for the use of statins with or without ezetimibe to reduce ASCVD events. Newer cholesterol lowering agents have been introduced for the management of hyperlipidemia to reduce ASCVD, but these therapies have not been tested in the CKD population except in secondary analyses of patients with primarily CKD stage 3. This review summarizes the role of hyperlipidemia in ASCVD and treatment strategies for hyperlipidemia in the CKD population.

The association of QRS duration with atrial fibrillation in a heart failure with preserved ejection fraction population: a pilot study.

BACKGROUND: Heart failure is a significant cause of morbidity and mortality, yet patient risk stratification may be difficult. Prevention or treatment of atrial fibrillation (AF) may be an important strategy in these patients that could positively affect their outcome. It has been demonstrated that in patients with systolic dysfunction, prolonged QRS duration (QRSd), an easily measured electrocardiographic parameter, is associated with AF. HYPOTHESIS: Prolonged QRSd is associated with an increase in prevalence of AF in patients with heart failure with preserved ejection fraction(HFPEF). METHODS: Between February 2006 and February 2009, 718 patients were discharged with a diagnosis of HF from the Dartmouth-Hitchcock Medical Center. Of these, 206 had EF ≥50% by echocardiography performed within 72 hours of admission. After exclusions, 82 patients remained, of which 25 had AF and 57 had sinus rhythm. Characteristics of the AF and sinus-rhythm patients were compared in this pilot study. RESULTS: After adjustment for age, prior diagnosis of HF, and left atrial area, there was a nonsignificant trend (odds ratio: 2.2, 95% CI of 0.3-17.2) for a QRSd >120 ms to be associated with AF. CONCLUSIONS: Similar to results in patients with systolic dysfunction, patients with preserved EF may have an association between a prolonged QRSd and AF.

Evaluation and Management of Pulmonary Hypertension in Kidney Transplant Candidates and Recipients: Concepts and Controversies.

Although cardiac evaluation before kidney transplantation commonly focuses on coronary artery disease, a comprehensive pretransplant cardiac evaluation must consider other prognostically important cardiac conditions including functional and structural heart disease. Pulmonary hypertension (PH) is increasingly recognized among patients with kidney failure and may be driven by left heart failure, high cardiac output from arteriovenous fistula, hypoxic lung diseases, and metabolic derangements associated with renal disease. In this article, we examine several key concepts and controversies relevant to optimizing the assessment and management of PH in kidney transplant candidates and recipients. First, categorizing PH according to underlying pathophysiologies, hemodynamic characteristics, and treatment responses as currently defined by the World Health Organization can be challenging in this population, but should be pursued to direct appropriate management. Second, echocardiographic PH (based on variable definitions) has been reported in 13% to 50% of selected pretransplant cohorts, but use of more precise diagnostic methods is needed to better define epidemiology and underlying etiologies. Third, although measures of PH have been associated with adverse patient and graft outcomes after kidney transplantation, pilot data suggest that PH may improve with successful transplantation. Fourth, recent advances in PH treatment in the general population focus on World Health Organization group 1 pulmonary arterial hypertension, and the efficacy of management strategies for any PH type in patients with renal failure is largely unproven. Broader prospective data, including attention to the impact of transplantation, are needed to advance understanding of the frequency, causes, and optimal management of PH in kidney transplant candidates and recipients.

Practice gaps in the care of mitral valve regurgitation: Insights from the American College of Cardiology mitral regurgitation gap analysis and advisory panel.

BACKGROUND: The revised 2014 American College of Cardiology (ACC)/American Heart Association valvular heart disease guidelines provide evidenced-based recommendations for the management of mitral regurgitation (MR). However, knowledge gaps related to our evolving understanding of critical MR concepts may impede their implementation. METHODS: The ACC conducted a multifaceted needs assessment to characterize gaps, practice patterns, and perceptions related to the diagnosis and treatment of MR. A key project element was a set of surveys distributed to primary care and cardiovascular physicians (cardiologists and cardiothoracic surgeons). Survey and other gap analysis findings were presented to a panel of 10 expert advisors from specialties of general cardiology, cardiac imaging, interventional cardiology, and cardiac surgeons with expertise in valvular heart disease, especially MR, and cardiovascular education. The panel was charged with assessing the relative importance and potential means of remedying identified gaps to improve care for patients with MR. RESULTS: The survey results identified several knowledge and practice gaps that may limit implementation of evidence-based recommendations for MR care. Specifically, half of primary care physicians reported uncertainty regarding timing of intervention for patients with severe primary or functional MR. Physicians in all groups reported that quantitative indices of MR severity were frequently not reported in clinical echocardiographic interpretations, and that these measurements were not consistently reviewed when provided in reports. In the treatment of MR, nearly 30% of primary care physician and general cardiologists did not know the volume of mitral valve repair surgeries by their reference cardiac surgeons and did not have a standard source to obtain this information. After review of the survey results, the expert panel summarized practice gaps into 4 thematic areas and offered proposals to address deficiencies and promote better alignment with the 2014 ACC/American Heart Association valvular disease guidelines. CONCLUSION: Important knowledge and skill gaps exist that may impede optimal care of the patient with MR. Focused educational and practice interventions should be developed to reduce these gaps.

Quantification of the variability associated with repeat measurements of left ventricular two-dimensional global longitudinal strain in a real-world setting.

BACKGROUND: Global longitudinal strain (GLS) derived from two-dimensional speckle-tracking is an emerging technology, but lack of industry standards limits its application. Prior studies support using this tool to identify subclinical disease through serial changes, but the variability introduced by a change in vendor or reader is not well defined. METHODS: Fifty study subjects were prospectively identified to include four subgroups to ensure a broad range of GLS: normal (n = 20), left ventricular hypertrophy (n = 10), ST-segment elevation myocardial infarction (n = 10), and systolic heart failure (n = 10). Raw data were obtained using equipment from two vendors during the same session, and GLS was analyzed using an offline workstation. Intraobserver and interobserver variation was measured using correlation coefficients, intraclass correlation coefficients, and Bland-Altman plots. RESULTS: GLS measurements were highly reproducible by the same reader or a different reader using vendor 1 and vendor 2 or comparing vendors (correlation coefficients and intraclass correlation coefficients ≥ 0.95). However, the Bland-Altman plots suggested that the variation in repeat GLS measurements may range from ± 2% to ± 5% on the basis of a change in vendor, reader, or both. CONCLUSIONS: The expected variation in GLS measurements associated with a change in vendor, reader, or both should be considered when making conclusions about significant changes in serial measurements.

Effect of preoperative pulmonary hypertension on outcomes in patients with severe aortic stenosis following surgical aortic valve replacement.

Pulmonary hypertension (PH) is prevalent in patients with aortic stenosis (AS); however, previous studies have demonstrated inconsistent results regarding the association of PH with adverse outcomes after aortic valve replacement (AVR). The goal of this study was to evaluate the effects of preoperative PH on outcomes after AVR. We performed a regional prospective cohort study using the Northern New England Cardiovascular Disease Study Group database to identify 1,116 consecutive patients from 2005 to 2010 who underwent AVR ± coronary artery bypass grafting for severe AS with a preoperative assessment of pulmonary pressures by right-sided cardiac catheterization. PH was defined as a mean pulmonary artery pressure of ≥25 mm Hg, with severity based on the pulmonary artery systolic pressure-mild, 35 to 44 mm Hg; moderate, 45 to 59 mm Hg; and severe, ≥60 mm Hg. We found that PH was present in 536 patients (48%). Postoperative acute kidney injury, low-output heart failure, and in-hospital mortality increased with worsening severity of PH. In multivariate logistic regression, severe PH was independently associated with postoperative acute kidney injury (adjusted odds ratio 4.1, 95% confidence interval [CI] 1.7 to 10, p = 0.002) and in-hospital mortality (adjusted odds ratio 6.9, 95% CI 2.5 to 19.1, p <0.001). There was a significant association between PH and decreased 5-year survival (adjusted log-rank p value = 0.006), with severe PH being associated with the poorest survival (adjusted hazard ratio 2.4, 95% CI 1.3 to 4.2, p = 0.003). In conclusion, severe PH in patients with severe AS is associated with increased rates of in-hospital adverse events and decreased 5-year survival after AVR.

Cardiac catheterization in the dialysis population in 2012: we know more, but much remains unknown.

Chronic kidney disease is now widely accepted as an independent risk factor for coronary disease and the dialysis population may represent the highest risk subgroup. Among all dialysis patients, a cardiac cause of mortality has been estimated at 40%. In addition, prior studies have demonstrated that when cardiac catheterization is obtained in a consecutive series of asymptomatic diabetic patients on dialysis the rates of coronary disease can approach 50%. However, the ability to define the problem continues to be greater than the ability to treat or prevent it. Coronary revascularization strategies have limitations in the general population which are amplified in the dialysis population. The ability to accurately diagnose an acute coronary syndrome is more difficult, clinical outcomes have a smaller margin of benefit, and technical challenges result in higher complication rates. Recent data demonstrate an inverse relationship between glomerular filtration rate and the risk of presenting with an acute myocardial infarction rather than unstable angina suggesting that patients with CKD may have a unique pathophysiologic profile that is more prone to plaque rupture. However, these "vulnerable" plaques typically are associated with stenoses <50% prior to rupture and are thus poor targets for revascularization and perhaps best treated with medical therapy. Although the benefits of revascularization may continue to outweigh the risks in the context of acute coronary syndromes, preventive strategies would have to overcome the lower margin of benefit and higher complication rates.

Regional patterns of dyssynchrony: lateral wall delay is desirable but not essential for left ventricular remodeling in biventricular pacing.

BACKGROUND: Tissue synchronization imaging (TSI), a parametric imaging technique based on tissue velocity imaging, often demonstrates patterns other than lateral delay in patients evaluated for cardiac resynchronization therapy (CRT). The prevalence of these patterns and their response to CRT has not been well described. We hypothesized that regional patterns of dyssynchrony might correlate with the extent of reverse remodeling. METHODS: A consecutive series of 32 patients underwent echocardiographic study prior to CRT implant and 3 months postimplant. TSI was used to color-code the time-to-peak positive systolic velocity at six basal and six mid-LV segments. Each patient was assigned to one of four groups based on the predominant location of greatest delay (≥ 2 segments): (1) posterolateral delay, (2) septal delay, (3) no dyssynchrony, or (4) other. RESULTS: Patients were classified as follows: posterolateral delay in 44% of patients (n = 14), septal delay in 28% (n = 9), no dyssynchrony in 16% (n = 5), and other pattern in 13% (n = 4). At 3-month follow-up, the group with the lateral delay pattern was associated with the greatest decrease in left ventricular end-systolic volume (LVESV) and the largest improvement in left ventricular ejection fraction (LVEF) (-45 mL and +9.3%, respectively, P < 0.05). The LVESV in the other three groups changed as follows: -24 mL (septal), -28 mL (no dyssynchrony), and -15 mL (other). Similar trends were observed for LVEF and left ventricular end-diastolic volume. CONCLUSIONS: Despite the presence of wide QRS and a left bundle branch block, the most delayed segment is not always the posterolateral wall. Posterolateral delay is associated with the best response to CRT, while other patterns respond at a lower magnitude.

A call to action: variability in guidelines for cardiac evaluation before renal transplantation.

BACKGROUND AND OBJECTIVES: Candidates for renal transplantation are at increased risk for complications related to cardiovascular disease; however, the optimal strategy to reduce this risk is not clear. The aim of this study was to evaluate the variability among existing guidelines for preoperative cardiac evaluation of renal transplant candidates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A consecutive series of renal transplant candidates (n=204) were identified, and four prominent preoperative cardiac evaluation guidelines, pertaining to this population, were retrospectively applied to determine the rate at which each guideline recommended cardiac stress testing. RESULTS: The rate of pretransplant cardiac stress testing would have ranged from 20 to 100% depending on which guideline was applied. The American Heart Association/American College of Cardiology (ACC/AHA) guideline resulted in the lowest rate of testing (20%). In our population, 178 study subjects underwent stress testing: 17 were found to have ischemia and 10 underwent revascularization. The ACC/AHA approach would have decreased the number of noninvasive tests from 178 to 39; it would have identified only 4 of the 10 patients who underwent revascularization. The three other guidelines (renal transplant-specific guidelines) recommended widespread pretransplant cardiac testing and thus identified nearly all patients who had ischemia on stress testing. CONCLUSIONS: The ACC/AHA perioperative guideline may be inadequate for identifying renal transplant candidates with coronary disease; however, renal transplant-specific guidelines may provoke significant overtesting. An intermediate approach based on risk factors specific to the ESRD population may optimize detection of coronary disease and limit testing.