Secondary Mitral Regurgitation: Updated Review with Focus on Percutaneous Interventional Management.

Secondary mitral regurgitation (SMR) is associated with increased mortality and heart failure hospitalizations. The management of heart failure patients with SMR is complex and requires a multidisciplinary Heart Team approach. Guideline-directed medical therapies remain fundamental, yet in a proportion of patients SMR persists. In the past decade, transcatheter edge-to-edge repair (TEER) has been shown to improve survival in patients with SMR who remain symptomatic despite medical therapy. Technical advancements across newer generations of devices, improved imaging, and greater operator expertise have collectively contributed to the increased safety and efficacy of this procedure over time. Various emerging transcatheter mitral valve repair and replacement devices are currently under investigation and may offer superior, complementary or synergistic treatment options in patients ineligible for TEER. This review provides a state-of-the-art overview regarding the diagnosis of SMR, and currently available transcatheter mitral valve interventions and describes a contemporary approach to the management of SMR.

Implications of the Use of Artificial Intelligence Predictive Models in Health Care Settings : A Simulation Study.

BACKGROUND: Substantial effort has been directed toward demonstrating uses of predictive models in health care. However, implementation of these models into clinical practice may influence patient outcomes, which in turn are captured in electronic health record data. As a result, deployed models may affect the predictive ability of current and future models. OBJECTIVE: To estimate changes in predictive model performance with use through 3 common scenarios: model retraining, sequentially implementing 1 model after another, and intervening in response to a model when 2 are simultaneously implemented. DESIGN: Simulation of model implementation and use in critical care settings at various levels of intervention effectiveness and clinician adherence. Models were either trained or retrained after simulated implementation. SETTING: Admissions to the intensive care unit (ICU) at Mount Sinai Health System (New York, New York) and Beth Israel Deaconess Medical Center (Boston, Massachusetts). PATIENTS: 130 000 critical care admissions across both health systems. INTERVENTION: Across 3 scenarios, interventions were simulated at varying levels of clinician adherence and effectiveness. MEASUREMENTS: Statistical measures of performance, including threshold-independent (area under the curve) and threshold-dependent measures. RESULTS: At fixed 90% sensitivity, in scenario 1 a mortality prediction model lost 9% to 39% specificity after retraining once and in scenario 2 a mortality prediction model lost 8% to 15% specificity when created after the implementation of an acute kidney injury (AKI) prediction model; in scenario 3, models for AKI and mortality prediction implemented simultaneously, each led to reduced effective accuracy of the other by 1% to 28%. LIMITATIONS: In real-world practice, the effectiveness of and adherence to model-based recommendations are rarely known in advance. Only binary classifiers for tabular ICU admissions data were simulated. CONCLUSION: In simulated ICU settings, a universally effective model-updating approach for maintaining model performance does not seem to exist. Model use may have to be recorded to maintain viability of predictive modeling. PRIMARY FUNDING SOURCE: National Center for Advancing Translational Sciences.

Functional Effects of Cardiomyocyte Injury in COVID-19.

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrated cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of interleukins (ILs) with clinical findings related to laboratory values in COVID-19 patients to identify plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes from healthy human subjects with SARS-CoV-2 in the absence and presence of IL-6 and IL-1ß. Infection resulted in increased numbers of multinucleated cells. Interleukin treatment and infection resulted in disorganization of myofibrils, extracellular release of troponin I, and reduced and erratic beating. Infection resulted in decreased expression of mRNA encoding key proteins of the cardiomyocyte contractile apparatus. Although interleukins did not increase the extent of infection, they increased the contractile dysfunction associated with viral infection of cardiomyocytes, resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health System show that a significant portion of COVID-19 patients without history of heart disease have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection might underlie heart disease in COVID-19 patients. IMPORTANCE SARS-CoV-2 infects multiple organs, including the heart. Analyses of hospitalized patients show that a substantial number without prior indication of heart disease or comorbidities show significant injury to heart tissue, assessed by increased levels of troponin in blood. We studied the cell biological and physiological effects of virus infection of healthy human iPSC-derived cardiomyocytes in culture. Virus infection with interleukins disorganizes myofibrils, increases cell size and the numbers of multinucleated cells, and suppresses the expression of proteins of the contractile apparatus. Viral infection of cardiomyocytes in culture triggers release of troponin similar to elevation in levels of COVID-19 patients with heart disease. Viral infection in the presence of interleukins slows down and desynchronizes the beating of cardiomyocytes in culture. The cell-level physiological changes are similar to decreases in left ventricular ejection seen in imaging of patients' hearts. These observations suggest that direct injury to heart tissue by virus can be one underlying cause of heart disease in COVID-19.

Prognostic value of left ventricular global longitudinal strain in mitral regurgitation: a systematic review.

Conventional echocardiographic assessment may overestimate the left ventricular (LV) function in mitral regurgitation (MR). LV global longitudinal strain (GLS) is more sensitive marker to detect subclinical LV dysfunction. Multiple studies have investigated the prognostic value of LV-GLS in MR to examine its potential to determine the timing and indication of intervention. This systematic review aimed to assess the prognostic value of LV-GLS in patients with mitral regurgitation (MR) to define its clinical applicability. PUBMED and EMBASE were queried through July 2021 to identify studies investigating the prognostic value of LV-GLS in MR. A total of 24 observational studies with 5267 patients were identified. Sixteen studies investigated for primary MR, 7 studies for secondary MR, and 1 study for both. Most studies included patients who underwent intervention. There was significant heterogeneity in patient population, intervention status, follow-up period, LV-GLS cutoff value, outcomes, and statistical methods among the studies. Meta-analysis was not performed considering the significant variability. With exception to 1 study, all studies demonstrated significant association between impaired LV-GLS and worse clinical and echocardiographic outcomes in primary MR. Prognostic value of LV-GLS in secondary MR was less certain due to inconsistent findings and limited reporting. LV-GLS is a promising parameter of prognostication in primary MR and can be considered as alternative to determine the timing of intervention. However, the optimal cutoff value remains unclear. The prognostic value of LV-GLS in secondary MR is less clear. Further large-scale prospective study is warranted before its routine clinical application.

Rationale and Design of the SOTA-P-CARDIA Trial (ATRU-V): Sotagliflozin in HFpEF Patients Without Diabetes.

Heart failure with preserved ejection fraction (HFpEF) is now the most common form of heart failure (HF). This syndrome is associated with an elevated morbi-mortality, and effective therapies are urgently needed. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are the first pharmacological class that has demonstrated to reduce hospitalization and cardiovascular mortality in large clinical trials in HFpEF. Furthermore, the dual SGLT 1/2 inhibitor sotagliflozin has shown a reduction in cardiovascular outcomes in diabetic HF patients, regardless of ejection fraction Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure (SOLOIST-WHF) Trial, and prevents the development of HF in patients with diabetes and chronic kidney disease Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) trial. The major objective of the Sotagliflozin in Heart Failure With Preserved Ejection Fraction Patients (SOTA-P-CARDIA) trial (NCT05562063) is to investigate whether the observed cardiorenal benefits of sotagliflozin in HF patients with diabetes can be extended to a non-diabetic population. The SOTA-P-CARDIA is a prospective, randomized, double-blinded, placebo-controlled study that will randomize non-diabetic patients with the universal definition of HFpEF (ejection fraction > 50% assessed the day of randomization). Qualifying patients will be randomized, in blocks of 4, to receive either sotagliflozin or placebo for a period of 6 months. The primary outcome is changes in left ventricular mass by cardiac magnetic resonance from randomization to end of the study between the groups. Secondary end points include changes in peak VO2; myocardial mechanics, interstitial myocardial fibrosis, and volume of epicardial adipose tissue; distance in the 6-min walk test; and quality of life. Finally, the authors expect that this trial will help to clarify the potential benefits of the use of sotagliflozin in non-diabetic HFpEF patients.

Perivalvular Extension of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Infective endocarditis (IE) following transcatheter aortic valve replacement (TAVR) has been associated with a dismal prognosis. However, scarce data exist on IE perivalvular extension (PEE) in such patients. METHODS: This multicenter study included 579 patients who had the diagnosis of definite IE at a median of 171 (53-421) days following TAVR. PEE was defined as the presence of an intracardiac abscess, pseudoaneurysm, or fistula. RESULTS: A total of 105 patients (18.1%) were diagnosed with PEE (perivalvular abscess, pseudoaneurysm, fistula, or a combination in 87, 7, 7, and 4 patients, respectively). A history of chronic kidney disease (adjusted odds ratio [ORadj], 2.08; 95% confidence interval [CI]: 1.27-3.41; P = .003) and IE secondary to coagulase-negative staphylococci (ORadj, 2.71; 95% CI: 1.57-4.69; P < .001) were associated with an increased risk of PEE. Surgery was performed at index IE episode in 34 patients (32.4%) with PEE (vs 15.2% in patients without PEE, P < .001). In-hospital and 2-year mortality rates among PEE-IE patients were 36.5% and 69.4%, respectively. Factors independently associated with an increased mortality were the occurrence of other complications (stroke post-TAVR, acute renal failure, septic shock) and the lack of surgery at index IE hospitalization (padj < 0.05 for all). CONCLUSIONS: PEE occurred in about one-fifth of IE post-TAVR patients, with the presence of coagulase-negative staphylococci and chronic kidney disease determining an increased risk. Patients with PEE-IE exhibited high early and late mortality rates, and surgery during IE hospitalization seemed to be associated with better outcomes.

Conventional versus modified delivery system technique in commissural alignment from the Evolut low-risk CT substudy.

OBJECTIVES: We assessed the impact of conventional delivery system (DS) insertion technique on "Hat-marker" orientation/commissural alignment in patients who underwent transcatheter aortic valve replacement (TAVR) in the Evolut Low Risk Trial CT substudy versus a modified technique. BACKGROUND: Unlike surgical aortic valve replacement, where alignment of the surgical valve commissures with native commissures can be achieved virtually 100% of the time, commissural alignment during TAVR is not achieved consistently. This may subsequently impact the feasibility of both coronary access and reintervention after TAVR. METHODS: "Hat-marker" orientations during deployment were characterized as outer curve (OC), center front (CF), inner curve, and center back. Severe commissure-to-CA overlap was 0-20°. "Hat-marker" orientations and CA overlap were compared to 240 patients from a single center using the modified 3-o'clock flush port DS technique. RESULTS: In the CT substudy in which conventional DS insertion was performed (flush port at 12 o'clock); 154/249 had both analyzable CT and procedural fluoroscopy to validate "Hat-marker" to C-tab/commissural orientation. On post-TAVR CT, Evolut valve commissural orientation and coronary artery (CA) ostia were identified. Compared to conventional DS technique in the CT substudy, the modified technique had higher rates of "Hat-marker" at OC/CF orientation, improved commissural alignment and reduced severe CA overlap; (left main, 14.2 vs. 27.9%; right coronary artery, 11.7 vs. 27.3% both, 5.0 vs. 13.6%; 1 or both CA, 20.8 vs. 41.6%, all p < 0.01). CONCLUSIONS: The modified technique improved initial "Hat-marker" orientation during Evolut deployment and resulted in better commissural alignment and reduced CA overlap.

Outcomes and feasibility of redo-TAVR after Sapien 3 Ultra TAVR in extremely-undersized versus nominally-sized annuli.

OBJECTIVES: To compare outcomes in Sapien 3 Ultra (S3U) transcatheter aortic valve replacement (TAVR) with extreme annular undersizing (EAU) versus nominal annular sizing (NAS). BACKGROUND: The Edwards S3U valve has reduced paravalvular leak (PVL) in TAVR but outcomes remain unknown in extremely undersized anatomy. Implanting a smaller S3U valve may facilitate future redo-TAVR but risk compromising hemodynamics. METHODS: From December 2019 to July 2021, 366 patients with native aortic stenosis underwent S3U TAVR. Patients with EAU (annular areas >430 mm2 for 23 mm or >546 mm2 for 26 mm) were compared to NAS (338-430 mm2 for 23 mm or 430-546 mm2 for 26 mm). In-hospital and 30-day outcomes, and redo-TAVR feasibility were determined. RESULTS: There were 79 (21.6%) EAU patients, with more bicuspid (p = 0.0014) and ≥moderate annular/left ventricular outflow tract calcification (p < 0.001). The EAU group had less annular oversizing than NAS group (23 mm: -8.2 ± 2.6% vs. 4.0 ± 7.0%, p < 0.001; 26 mm: -8.9 ± 2.2% vs. 6.7 ± 6.9%, p < 0.001), more balloon overfilling (71.3% vs. 11.6%, p < 0.001), and postdilatation (15.0% vs. 5.8%, p = 0.016). No differences were found in in-hospital or 30-day mortality and stroke (p > 0.05). Mild PVL (13.4% EAU vs. 11.5% NAS, p = 0.56) and mean gradients (23 mm: 13.0 ± 4.5 vs. 14.1 ± 5.4 mmHg, p = 0.40; 26 mm: 11.4 ± 4.1 vs. 11.5 ± 3.9 mmHg, p = 1.0) were similar at 30 days. Had the EAU group undergone NAS with the larger Sapien 3/S3U, by computed tomography analysis simulating 80:20 or 90:10 target implant depth, 33.3%-60.9% (vs. 4.3%-23.2%) would not be feasible for redo-TAVR due to high risk of coronary obstruction. CONCLUSIONS: In this first report of EAU with S3U TAVR, similar excellent short-term outcomes can be achieved compared to NAS, and may preserve future redo-TAVR option.

Epigenetic Modifications and Non-Coding RNA in Diabetes-Mellitus-Induced Coronary Artery Disease: Pathophysiological Link and New Therapeutic Frontiers.

Diabetes mellitus (DM) is a glucose metabolism disorder characterized by chronic hyperglycemia resulting from a deficit of insulin production and/or action. DM affects more than 1 in 10 adults, and it is associated with an increased risk of cardiovascular morbidity and mortality. Cardiovascular disease (CVD) accounts for two thirds of the overall deaths in diabetic patients, with coronary artery disease (CAD) and ischemic cardiomyopathy as the main contributors. Hyperglycemic damage on vascular endothelial cells leading to endothelial dysfunction represents the main initiating factor in the pathogenesis of diabetic vascular complications; however, the underlying pathophysiological mechanisms are still not entirely understood. This review addresses the current knowledge on the pathophysiological links between DM and CAD with a focus on the role of epigenetic modifications, including DNA methylation, histone modifications and noncoding RNA control. Increased knowledge of epigenetic mechanisms has contributed to the development of new pharmacological treatments ("epidrugs") with epigenetic targets, although these approaches present several challenges. Specific epigenetic biomarkers may also be used to predict or detect the development and progression of diabetes complications. Further studies on diabetes and CAD epigenetics are needed in order to identify possible new therapeutic targets and advance personalized medicine with the prediction of individual drug responses and minimization of adverse effects.

Using Clinical and Echocardiographic Characteristics to Characterize the Risk of Ischemic Stroke in Patients with COVID-19.

BACKGROUND: COVID-19 has been associated with an increased incidence of ischemic stroke. The use echocardiography to characterize the risk of ischemic stroke in patients hospitalized with COVID-19 has not been explored. METHODS: We conducted a retrospective study of 368 patients hospitalized between 3/1/2020 and 5/31/2020 who had laboratory-confirmed infection with SARS-CoV-2 and underwent transthoracic echocardiography during hospitalization. Patients were categorized according to the presence of ischemic stroke on cerebrovascular imaging following echocardiography. Ischemic stroke was identified in 49 patients (13.3%). We characterized the risk of ischemic stroke using a novel composite risk score of clinical and echocardiographic variables: age <55, systolic blood pressure >140 mmHg, anticoagulation prior to admission, left atrial dilation and left ventricular thrombus. RESULTS: Patients with ischemic stroke had no difference in biomarkers of inflammation and hypercoagulability compared to those without ischemic stroke. Patients with ischemic stroke had significantly more left atrial dilation and left ventricular thrombus (48.3% vs 27.9%, p = 0.04; 4.2% vs 0.7%, p = 0.03). The unadjusted odds ratio of the composite novel COVID-19 Ischemic Stroke Risk Score for the likelihood of ischemic stroke was 4.1 (95% confidence interval 1.4-16.1). The AUC for the risk score was 0.70. CONCLUSIONS: The COVID-19 Ischemic Stroke Risk Score utilizes clinical and echocardiographic parameters to robustly estimate the risk of ischemic stroke in patients hospitalized with COVID-19 and supports the use of echocardiography to characterize the risk of ischemic stroke in patients hospitalized with COVID-19.

Temporal Trends, Characteristics, and Outcomes of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Procedural improvements combined with the contemporary clinical profile of patients undergoing transcatheter aortic valve replacement (TAVR) may have influenced the incidence and outcomes of infective endocarditis (IE) following TAVR. We aimed to determine the temporal trends, characteristics, and outcomes of IE post-TAVR. METHODS: Observational study including 552 patients presenting definite IE post-TAVR. Patients were divided in 2 groups according to the timing of TAVR (historical cohort [HC]: before 2014; contemporary cohort [CC]: after 2014). RESULTS: Overall incidence rates of IE were similar in both cohorts (CC vs HC: 5.45 vs 6.52 per 1000 person-years; P = .12), but the rate of early IE was lower in the CC (2.29‰ vs 4.89‰, P < .001). Enterococci were the most frequent microorganism. Most patients presented complicated IE ( CC: 67.7%; HC: 69.6%; P = .66), but the rate of surgical treatment remained low (CC: 20.7%; HC: 17.3%; P = .32). The CC exhibited lower rates of in-hospital acute kidney injury (35.1% vs 44.6%; P = .036) and in-hospital (26.6% vs 36.4%; P = .016) and 1-year (37.8% vs 53.5%; P < .001) mortality. Higher logistic EuroScore, Staphylococcus aureus etiology, and complications (stroke, heart failure, and acute renal failure) were associated with in-hospital mortality in multivariable analyses (P < .05 for all). CONCLUSIONS: Although overall IE incidence has remained stable, the incidence of early IE has declined in recent years. The microorganism, high rate of complications, and very low rate of surgical treatment remained similar. In-hospital and 1-year mortality rates were high but progressively decreased over time.

Insights into functional mitral regurgitation using transillumination rendering.

Secondary mitral regurgitation has been originally explained by tethering of the structurally normal mitral leaflets or by mitral annular dilation after atrial remodeling. Advances in echocardiography have provided more insights into functional anatomy of the mitral valve leaflets as active participants in this entity.

Cusp Overlap Technique: Should It Become the Standard Implantation Technique for Self-expanding Valves?

PURPOSE OF REVIEW: Accurate imaging of the aortic root during valve implantation is crucial for proper prosthesis positioning during TAVR. The purpose of this review was to determine if routine use of the cusp-overlap view should be adopted for self-expanding valves. RECENT FINDINGS: The use of the cusp-overlap view with the Evolut, Portico, ACURATE neo/neo2, and JenaValve systems is associated with lower post-procedural new permanent pacemaker implantation rates when compared with the standard 3-cusp view, presumably due to more precise valve implantation relative to the conduction system by the non-coronary cusp. By elongating the left ventricular outflow tract and accentuating the right-non commissure in the center of the fluoroscopic view, the cusp-overlap technique allows operators to more precisely control the prosthesis implant depth during self-expanding valve deployment. While the early experience with this approach in Evolut TAVR has been promising, the results of larger studies with longer follow-up across multiple self-expanding systems are warranted.

Anatomic classification of mitral annular calcification for surgical and transcatheter mitral valve replacement.

BACKGROUND AND AIM OF THE STUDY: A systematic approach to quantify mitral annular calcification (MAC) in all-comers by multidetector computed tomography (MDCT) is essential to guide treatment, but lacking. METHODS: From September 2015 to July 2019, 82 patients with MAC underwent MDCT at two institutions to evaluate for surgical mitral valve replacement (SMVR), transcatheter mitral valve replacement (TMVR), or medical management. Type 1 MAC was defined as <270° annular calcium and Type 2 as ≥270°. Absence/presence of predicted left ventricular outflow tract (LVOT) obstruction with virtual valve placement was used to further define Type 2 MAC into 2A/B for our treatment algorithm. RESULTS: Type 1 MAC was present in 51.2%, Type 2A in 18.3%, and Type 2B in 30.5%. Operable Type 1 patients (50.0%) underwent hybrid transatrial TMVR or SMVR. Type 2A underwent a variety of treatments, and Type 2B surgical candidates (40.0%) underwent hybrid transatrial TMVR secondary to difficult suture anchoring with significant MAC and predicted LVOT obstruction. At a follow-up of 29.6 ± 12.0 months, mortality was 42.7% with 46.3% in the intervention group and 39.0% in the medical group (p = 0.47). All percutaneous TMVR patients expired. This translated to a disproportionate number of Type 2A deaths (80.0% with intervention), but all were high/extreme surgical risk. The hybrid TMVR group consisted of 95.0% Type 1/2B patients and had a lower Society of Thoracic Surgeons predicted risk of operative mortality (7.4% vs. 9.2%, p = 0.43)/mortality. CONCLUSIONS: The highest mortality was seen in percutaneous TMVR Type 2A MAC patients, but they were at the greatest risk. Here we provide an objective MAC treatment algorithm for all-comers based on operability/anatomy.

Recent clinical trials in valvular heart diseases.

PURPOSE OF REVIEW: In recent years, no other field of cardiology has experienced a greater influx of transformational therapeutic options as valvular heart disease. The present review discusses the landmark trials published in the last 18 months that have shaped the modern day management of valvular heart diseases. RECENT FINDINGS: There have been several landmark trials in recent years, which have expanded the indications for transcatheter aortic valve replacement to low-risk surgical patients and the use of MitraClip for patients with functional mitral regurgitation. Options for transcatheter management of right-sided valvular disease also continue to evolve, including promising results from early feasibility studies. SUMMARY: The development of novel transcatheter therapies for valvular heart disease has expanded the armamentarium of physicians treating patients with valvular heart disease. The present review will focus on the recent (within 2 years) trials in this field of interest.

Radioprotective strategies for interventional echocardiographers during structural heart interventions.

OBJECTIVE: We investigated radioprotective strategies for the interventional echocardiographer (IE) during structural heart interventions in comparison with the interventional cardiologist (IC). BACKGROUND: Structural heart interventions are expanding in complexity with increased reliance on IE. Recent reports have demonstrated concerning exposure and higher radiation to the IE. METHODS: We monitored 32 structural interventions - 19 transcatheter aortic valve replacements (TAVR), 6 transcatheter mitral valve repairs, 5 paravalvular leak closures, and 2 atrial septal defect closures. Seventeen utilized transesophageal echocardiography (TEE) while 15 used transthoracic echocardiography (TTE). Members of the IC and IE teams wore multiple dosimeters on different sites of the body to measure radiation dose to the total body, lens of the eye, and hand. During each case, IE utilized dedicated radiation shielding. RESULTS: Mean doses were higher for the primary IC than the primary IE: IC#1-99, 222, 378; IE#1-48, 52, 416 (body, lens, and hand doses in µSv). IE radioprotective strategies were able to reduce body and lens doses compared to IC during both TTE and TEE-guided procedures. Hand equivalent dose remained higher for the IE driven by exposure during TEE-guided procedures (IC#1 294 vs. IE#1 676 µSv). In a subgroup using radioprotective drapes during TTE-guided TAVR, IC dose was reduced without effect on the IE. CONCLUSIONS: Radiation exposure during structural heart interventions is concerning. With dedicated shielding, IE received lower doses to the body and lens than IC. Further optimization of structural suite design and shielding is needed.

The incidence and prognostic implications of worsening right ventricular function after surgical or transcatheter aortic valve replacement: insights from PARTNER IIA.

Aims: In patients randomized to transcatheter or surgical aortic valve replacement (TAVR, SAVR), we sought to determine whether SAVR is associated with worsening right ventricular (RV) function and whether RV deterioration is associated with mortality. Methods and results: In 1376 patients from PARTNERIIA with paired baseline and 30-day core lab echocardiograms, worsening RV function was defined as decline by at least one grade from baseline to 30 days. Our primary outcome was all-cause mortality from 30 days to 2 years. Among 744 patients with TAVR, 62 (8.3%) had worsening RV function, compared with 156 of 632 patients with SAVR (24.7%) (P < 0.0001). In a multivariable model, SAVR [odds ratio (OR) 4.05, 95% confidence interval (CI) 2.55-6.44], a dilated RV (OR 2.38, 95% CI 1.37-4.14), and more than mild tricuspid regurgitation (TR) (OR 2.58, 95% CI 1.25-5.33) were associated with worsening RV function. There were 169 deaths, and patients with worsening RV function had higher all-cause mortality [hazard ratio (HR) 1.98, 95% CI 1.40-2.79]. This association remained robust after adjusting for clinical and echocardiographic variables. Among patients with worsening RV function, there was no mortality difference between TAVR and SAVR (HR 1.16, 95% CI 0.61-2.18). The development of moderate or severe RV dysfunction from baseline normal RV function conferred the worst prognosis (HR 2.87, 95% CI 1.40-5.89). Conclusion: After aortic valve replacement, worsening RV function is more common in patients with baseline RV dilation, more than mild TR, and in patients treated with SAVR. Worsening RV function and the magnitude of deterioration have important prognostic implications.

Soluble Urokinase Receptor and Chronic Kidney Disease.

BACKGROUND: Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS: We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m(2) of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS: A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was -0.9 ml per minute per 1.73 m(2) among participants in the lowest quartile of suPAR levels as compared with -4.2 ml per minute per 1.73 m(2) among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (≥ 90 ml per minute per 1.73 m(2)) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m(2), the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS: An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation and others.).

Ostial right coronary chronic total occlusion: Transesophageal echocardiographic guidance for retrograde aortic re-entry.

As antegrade options are limited, intervention upon the ostial right coronary artery (RCA) chronic total occlusion (CTO) warrants a retrograde approach. Landmarks for an aggressive approach are concerning as passage of stiff guidewires or electrocautery near the RCA ostium may result in wire passage into structures other than the aorta. We report the first use of transesophageal echocardiography (TEE) to assist retrograde passage of a guidewire into the aorta. For the ostial RCA CTO, TEE guidance may be considered to assist retrograde passage of aggressive guidewires into the aorta.