Five-year outcomes of transcatheter reduction of significant mitral regurgitation in high-surgical-risk patients.

OBJECTIVES: This study evaluates the 5-year clinical outcomes of transcatheter mitral valve (MV) repair with the MitraClip device in patients at high risk for MV surgery treated in the Endovascular Valve Edge-to-Edge Repair (EVEREST) II High Risk Study (HRS). METHODS: Patients with mitral regurgitation (MR) 3+ or 4+ and predicted surgical mortality risk ≥12% or surgeon assessment based on prespecified high-risk factors were enrolled. Patients prospectively consented to 5 years of follow-up. RESULTS: At 5 years, clinical follow-up was achieved in 90% of 78 enrolled patients. The rate of postprocedural adverse events declined from 30 days to 1 year follow-up and was stable thereafter through 5 years. Two patients (2.6%) developed mitral stenosis (MS). Two patients underwent MV surgery, including one due to MS. A total of 42 deaths were reported through 5 years. Effectiveness measures at 5 years showed reductions in MR severity to ≤2+ in 75% of patients (p=0.0107), left ventricular (LV) end-diastolic volume (-38.2 mL; 95% CI -55.0 to -21.4; p<0.0001) and LV end-systolic volume (-14.6 mL; 95% CI -27.7 to -1.5; p=0.0303) compared with baseline. The New York Heart Association (NYHA) functional class improved from baseline to 5 years (p<0.005), and septal-lateral annular dimensions remained stable with no indication of mitral annular dilation through 5 years. CONCLUSIONS: The EVEREST II HRS demonstrated long-term safety and efficacy of MitraClip in high-surgical-risk patients through 5 years. The observed mortality was most likely a consequence of the advanced age and comorbidity profile of the enrolled patients, while improvements in NYHA class in surviving patients were durable through long-term follow-up. TRIAL REGISTRATION NUMBER: NCT01940120.

Observed to expected 30-day mortality as a benchmark for transcatheter aortic valve replacement.

OBJECTIVE: The observed-to-expected 30-day mortality ratio (O:E ratio) is a standard metric by which transcatheter aortic valve replacement (TAVR) trials have been evaluated. Early TAVR trials consistently demonstrated O:E ratio less than 0.6 after TAVR when based on the Society for Thoracic Surgery Predicted Risk of Mortality (STS-PROM) for surgical aortic valve replacement. Recent published results from the Transcatheter Valve Therapy (TVT) Registry have demonstrated O:E ratios of 1.0. We evaluated our own O:E ratios for TAVR to investigate this discordance. METHODS: Data were collected prospectively for TAVR patients from 2008 through 2015 (N = 546) and were reviewed retrospectively. The observed mortality and STS-PROM were calculated to formulate O:E ratios and were compared over a variety of subgroups. RESULTS: Overall, the O:E ratio for 30-day mortality was 0.4 and significantly less than 1 (P < .001; 95% confidence interval, 0.25-0.63). The O:E ratio relationship remained less than 0.5 for patients with low (STS-PROM < 4), moderate (STS-PROM = 4-8) and high risk (STS-PROM > 8). The O:E ratio was significantly higher for transapical patients (O:E ratio = 0.8) when compared with transfemoral patients (O:E ratio = 0.2). Lastly, O:E ratios for both commercial (O:E ratio = 0.5) and research (O:E ratio = 0.3) patients were similar (P = .337), and both were significantly less than 1 (P = .007 and P < .001, respectively). CONCLUSIONS: The STS-PROM consistently overestimated 30-day mortality after TAVR. Achieving an O:E ratio less than 0.6 may be a realistic goal for all TAVR programs. While an accurate and specific risk calculator for 30-day mortality after TAVR remains to be established, our data suggest that current TVT results are not acceptable for commercial TAVR and that programs with an O:E ratio greater than 0.6, based on the STS-PROM, should reevaluate internal processes to improve their results.

Anesthetic Considerations for the Transcatheter Management of Mitral Valve Disease.

The development of transcatheter interventions to provide a minimally invasive alternative to open surgical repair has revolutionized the care of patients with valvular heart disease. Recently, this technology has been expanded to allow for the treatment of pathology of the mitral valve. This review discusses the anesthetic considerations for patients presenting for transcatheter management of mitral valve disease, including transcatheter mitral valve replacement (TMVR) and transcatheter mitral valve repair (TMVRep). The initial focus is on the current literature on transcatheter interventions for mitral valve pathologies as well as current and developing technology for TMVR and TMVRep. The authors' institutional experience with anesthetic management for the TMVR and TMVRep procedures is described, including potential pitfalls and complications, concluding with a discussion of the role of transesophageal echocardiography in the care of this patient population.

Outcomes After the MitraClip Procedure in Patients at Very High Risk for Conventional Mitral Valve Surgery.

OBJECTIVE: Approximately 50% of patients with severe symptomatic mitral regurgitation are deemed too high risk for surgery. The MitraClip procedure is a viable option for this population. Our goal was to assess outcomes and survival of patients who underwent the MitraClip procedure at an institution where mitral valve surgery is routinely performed. METHODS: A retrospective study of patients undergoing the MitraClip procedure was performed. Baseline characteristics, perioperative outcomes, and follow-up echocardiographic and clinical outcomes were examined. Primary end point was survival. Secondary end points included technical failure (residual 3/4+ mitral regurgitation), reoperation, New York Heart Association symptoms, 30-day mortality, and other clinical outcomes. Predictors of mortality were determined using multivariable regression analysis. RESULTS: Fifty consecutive patients underwent the MitraClip procedure during the 4-year period. The average age was 83, the Society of Thoracic Surgeons predicted risk of mortality mean was 9.4%, 88% (44/50) had New York Heart Association III/IV symptoms, 86% (43/50) had 4+ mitral regurgitation, and 72% (36/50) had degenerative mitral disease etiology. Echocardiographic data (median [interquartile range] follow-up = 43 [26-392]) showed that 86% (43/50) of patients had 2+ or less mitral regurgitation. Sixty percent (24/40) had New York Heart Association I/II symptoms at last follow-up. Predictors of mortality were higher Society of Thoracic Surgeons predicted risk of mortality (P = 0.042, hazard ratio = 1.098) and previous cardiac surgery (P = 0.013, hazard ratio = 3.848). Survival at 1 and 2 years was 75% and 63%, respectively. CONCLUSIONS: Many patients with mitral valve regurgitation who are high risk for open surgery can be treated with the MitraClip procedure. In our study, most patients (86%) had a technically successful operation and postoperative outcomes including survival were acceptable.

Reversing the "Risk-Treatment Paradox" of Bleeding in Patients Undergoing Percutaneous Coronary Intervention: Risk-Concordant Use of Bleeding Avoidance Strategies Is Associated With Reduced Bleeding and Lower Costs.

Background Bleeding is a common, morbid, and costly complication of percutaneous coronary intervention. While bleeding avoidance strategies ( BAS ) are effective, they are used paradoxically less in patients at high risk of bleeding. Whether a patient-centered approach to specifically increase the risk-concordant use of BAS and, thus, reverse the risk-treatment paradox is associated with reduced bleeding and costs is unknown. Methods and Results We implemented an intervention to reverse the bleeding risk-treatment paradox at Barnes-Jewish Hospital, St. Louis, MO, and examined: (1) the temporal trends in BAS use and (2) the association of risk-concordant BAS use with bleeding and hospital costs of percutaneous coronary intervention. Among 3519 percutaneous coronary interventions, there was a significantly increasing trend ( P=0.002) in risk-concordant use of BAS . The bleeding incidence was 2% in the risk-concordant group versus 9% in the risk-discordant group (absolute risk difference, 7%; number needed to treat, 14). Risk-concordant BAS use was associated with a 67% (95% confidence interval, 52-78%; P<0.001) reduction in the risk of bleeding and a $4738 (95% confidence interval, 3353-6122; P<0.001) reduction in per-patient percutaneous coronary intervention hospitalization costs (21.6% cost-savings). Conclusions In this study, patient-centered care directly aimed to make treatment-related decisions based on predicted risk of bleeding, led to more risk-concordant use of BAS and reversal of the risk-treatment paradox. This, in turn, was associated with a reduction in bleeding and hospitalization costs. Larger multicentered studies are needed to corroborate these results. As clinical medicine moves toward personalization, both patients and hospitals can benefit from a simple practice change that encourages objectivity and mitigates variability in care.

Acute right ventricular failure and pulseless electrical activity arrest following auto-transfusion of blood.

Air embolism is a rare but potentially catastrophic complication of interventional procedures. The occurrence of acute right ventricular dysfunction during intraoperative auto-transfusion of blood, presumably related to pulmonary embolism of agitated air microbubbles and microthrombi, is less commonly recognized. We report a case of auto-transfusion complicated by acute right ventricular failure and pulseless electrical activity arrest. Auto-transfusion of recovered blood is a practical solution to reduce need for post-procedure allogenic transfusions. Although such interventions are frequently performed without complications, they do have inherent risks that should be readily acknowledged. This case clearly describes a severe complication and sequelae of auto-transfusion. .

Novel Patient-Centered Approach to Facilitate Same-Day Discharge in Patients Undergoing Elective Percutaneous Coronary Intervention.

BACKGROUND: Same-day discharge (SDD) after elective percutaneous coronary intervention is safe, less costly, and preferred by patients, but it is usually performed in low-risk patients, if at all. To increase the appropriate use of SDD in more complex patients, we implemented a "patient-centered" protocol based on risk of complications at Barnes-Jewish Hospital. METHODS AND RESULTS: Our objectives were as follows: (1) to evaluate time trends in SDD; (2) to compare (a) mortality, bleeding, and acute kidney injury, (b) patient satisfaction, and (c) hospital costs by SDD versus no SDD (NSDD); and (3) to compare SDD eligibility by our patient-centered approach versus Society for Cardiovascular Angiography and Interventions guidelines. Our patient-centered approach was based on prospectively identifying personalized bleeding, mortality, and acute kidney injury risks, with a personalized safe contrast limit and mitigating those risks. We analyzed Barnes-Jewish Hospital's National Cardiovascular Data Registry CathPCI Registry data from July 1, 2009 to September 30, 2015 (N=1752). SDD increased rapidly from 0% to 77% (P<0.001), independent of radial access. Although SDD patients were comparable to NSDD patients, SDD was not associated with adverse outcomes (0% mortality, 0% bleeds, and 0.4% acute kidney injury). Patient satisfaction was high with SDD. Propensity score-adjusted costs were $7331 lower/SDD patient (P<0.001), saving an estimated $1.8 million annually. Only 16 patients (6.95%) met the eligibility for SDD by Society for Cardiovascular Angiography and Interventions guidelines, implying our patient-centered approach markedly increased SDD eligibility. CONCLUSIONS: With a patient-centered approach, SDD rapidly increased and was safe in 75% of patients undergoing elective percutaneous coronary intervention, despite patient complexity. Patient satisfaction was high, and hospital costs were lower. Patient-centered decision making to facilitate SDD is an important opportunity to improve the value of percutaneous coronary intervention.

Mechanical Circulatory Support in Acute Decompensated Heart Failure and Shock.

An array of interventional therapeutics is available in the modern era, with uses depending on acute or chronic situations. This article focuses on support in acute decompensated heart failure and cardiogenic shock, including intra-aortic balloon pumps, continuous aortic flow augmentation, and extra-corporeal membrane oxygenation.

Left Ventricular Unloading by Impella Device Versus Surgical Vent During Extracorporeal Life Support.

BACKGROUND: Patients supported with extracorporeal life support (ECLS) can experience severe complications from increased left ventricular (LV) afterload. The Impella (Abiomed, Danvers, MA) percutaneous ventricular assist device (PVAD) may offer an attractive option for unloading the LV in these patients. This study describes the efficacy and outcomes of PVAD use during ECLS compared with surgically placed LV vent. METHODS: In this retrospective study, we reviewed patients supported by ECLS with PVAD or surgical LV vent for cardiogenic shock between April 2010 and May 2016. Included were 23 patients with PVADs and 22 with surgical vents. Patients' baseline characteristics, hemodynamic data, and outcomes were collected immediately preceding combined support initiation, at 48 hours, intensive care unit discharge, and 30 days. RESULTS: After 48 hours, pulmonary artery diastolic pressure was significantly reduced in the PVAD (23.3 ± 8.4 vs 15.6 ± 4.2, p = 0.02) and surgical vent groups (20.1 ± 5.9 vs 15.6 ± 5.4, p = 0.01), and radiographic evidence of pulmonary edema was reduced or unchanged in 90% of PVAD patients and in 76% of surgical vent patients. The primary end points of survival to 30 days (43% vs 32%, p = 0.42) and intensive care unit discharge (35% vs 23%, p = 0.37) were not different between the two methods of support. The PVAD and surgical vent groups were also not significantly different in the rate of vascular complications or in the number decannulated from ECLS and transitioned to durable LV assist device. CONCLUSIONS: PVAD use in ECLS patients is an effective means of LV unloading and preventing worsened pulmonary edema, with outcomes and complications that are comparable to surgical LV vent.

Learning Alternative Access Approaches for Transcatheter Aortic Valve Replacement: Implications for New Transcatheter Aortic Valve Replacement Centers.

BACKGROUND: Smaller transcatheter aortic valve replacement (TAVR) delivery systems have increased the number of patients eligible for transfemoral procedures while decreasing the need for transaortic (TAo) or transapical (TA) access. As a result, newer TAVR centers are likely to have less exposure to these alternative access techniques, making it harder to achieve proficiency. The purpose of this study was to evaluate the learning curve for TAVR approaches and compare perioperative outcomes. METHODS: From January 2008 to December 2014, 400 patients underwent TAVR (transfemoral, n = 179; TA, n = 120; and TAo, n = 101)). Learning curves were constructed using metrics of contrast utilization, procedural, and fluoroscopy times. Outcomes during the learning curve were compared with after proficiency was achieved. RESULTS: Depending on the metric, learning curves for all three routes differed slightly but all demonstrated proficiency by the 50th case. There were no significant differences in procedural times whereas improvements in contrast use were most notable for TA (69 ± 40 mL versus 50 ± 23 mL, p = 0.002). For both TA and TAo, fewer patients received transfusions once proficiency was reached (62% versus 34%, p = 0.003, and 42% versus 14%, p = 0.002, respectively). No differences in 30-day or 1-year mortality were seen before or after proficiency was reached for any approach. CONCLUSIONS: The learning curves for TA and TAo are distinct but technical proficiency begins to develop by 25 cases and becomes complete by 50 cases for both approaches. Given the relatively low volume of alternative access, achieving technical proficiency may take significant time. However, technical proficiency had no effect on 30-day or 1-year mortality for any access approach.

Treatment of Higher-Risk Patients With an Indication for Revascularization: Evolution Within the Field of Contemporary Percutaneous Coronary Intervention.

Patients with severe coronary artery disease with a clinical indication for revascularization but who are at high procedural risk because of patient comorbidities, complexity of coronary anatomy, and/or poor hemodynamics represent an understudied and potentially underserved patient population. Through advances in percutaneous interventional techniques and technologies and improvements in patient selection, current percutaneous coronary intervention may allow appropriate patients to benefit safely from revascularization procedures that might not have been offered in the past. The burgeoning interest in these procedures in some respects reflects an evolutionary step within the field of percutaneous coronary intervention. However, because of the clinical complexity of many of these patients and procedures, it is critical to develop dedicated specialists within interventional cardiology who are trained with the cognitive and technical skills to select these patients appropriately and to perform these procedures safely. Preprocedural issues such as multidisciplinary risk and treatment assessments are highly relevant to the successful treatment of these patients, and knowledge gaps and future directions to improve outcomes in this emerging area are discussed. Ultimately, an evolution of contemporary interventional cardiology is necessary to treat the increasingly higher-risk patients with whom we are confronted.

Preoperative pulmonary function tests predict mortality after surgical or transcatheter aortic valve replacement.

OBJECTIVES: To determine the role of preoperative pulmonary function tests (PFTs) in patients with aortic stenosis (AS) evaluated for aortic valve replacement (AVR), and to evaluate the association between lung disease and mortality in specific subgroups. METHODS: Between 2008 and 2013, 535 patients with preoperative PFTs underwent AVR (transcatheter AVR [TAVR], n = 246; surgical AVR [SAVR], n = 289). The severity of lung disease determined by the Society of Thoracic Surgeons (STS) definition was evaluated in those with and without a clinical suspicion for lung disease (smoking, inhaled steroids/bronchodilators, or home oxygen). The association between lung disease and 1-year mortality was evaluated. RESULTS: Of the 186 patients (35%) without suspected lung disease, 39 (21%) had moderate/severe lung disease by PFT analysis. Among all patients, 1-year mortality was 12% in those with no lung disease, 17% in those with no mild lung disease, 22% in those with moderate lung disease, and 31% in those with severe lung disease (P < .001, log-rank test). After adjustment, moderate/severe lung disease was associated with increased 1-year mortality (adjusted hazard ratio, 2.07; 95% confidence interval, 1.30-3.29; P = .002); this association was not altered by smoking history, suspicion of lung disease, New York Heart Association class, or AVR type (interaction P value nonsignificant for all). CONCLUSIONS: In patients with AS evaluated for AVR, the STS risk score is significantly influenced by the severity of lung disease, which is determined predominantly by PFT results. Even when lung disease is not suspected, PFTs are abnormal in many patients undergoing AVR. Moderate/severe lung disease, diagnosed predominantly by PFTs, is an independent predictor of mortality after SAVR or TAVR. Collectively, these findings suggest that PFTs should be a routine part of the risk stratification of patients considered for AVR.

No reflow leading to catastrophic hemodynamic collapse in a patient with severe aortic stenosis and its management.

We report a case of an 87-year-old female who underwent percutaneous coronary intervention (PCI) for non-ST elevation myocardial infarction while she was being worked up for transcatheter aortic valve procedure. Hemodynamic compromise occurred during the PCI, which could only be mitigated by doing a balloon aortic valvuloplasty and Impella™ insertion. This case report will help in preparedness for any untoward events in patients with aortic stenosis and undergoing percutaneous coronary intervention.

Impact of intravascular ultrasound on the long-term clinical outcomes in the treatment of coronary ostial lesions.

OBJECTIVES: To evaluate the long-term outcomes of patients with ostial lesions who underwent percutaneous coronary intervention (PCI) with and without the use of intravascular ultrasound (IVUS). BACKGROUND: A higher rate of adverse cardiac events is associated with PCI of ostial lesions as compared with nonostial disease. METHODS: From 7/2002 to 8/2010, 225 patients with 233 coronary ostial lesions underwent PCI with (n = 82) and without (n = 143) IVUS guidance. Ostial lesions included both native aorto-ostial or major coronary vessel (left anterior descending, left circumflex, and ramus intermedius) lesions. Clinical outcomes [cardiovascular death, myocardial infarction (MI), and target lesion revascularization (TLR)] at a mean follow-up of 4.2 ± 2.5 years were compared between patients undergoing PCI of an ostial lesion with and without use of IVUS using univariate and propensity score adjusted analyses. RESULTS: Aorto-ostial lesions (n = 109) comprised 47% of lesions, whereas the remaining lesions (53%) involved major coronary vessels. After propensity score adjustment, IVUS use was associated with lower rates of the composite of cardiovascular death, MI, or TLR (HR 0.54, 95% CI 0.29-0.99; P = 0.04), composite MI or TLR (HR 0.39, 95% CI 0.18-0.83; P = 0.01), and MI (HR 0.31, 95% CI 0.11-0.85; P = 0.02) as compared with no IVUS. The use of IVUS was also associated with a trend towards a lower rate of TLR (HR 0.42, 95% CI 0.17-1.02; P = 0.06). CONCLUSIONS: PCI of coronary ostial lesions with the use of IVUS was associated with significantly lower rates of adverse cardiac events.

Clinical and Functional Outcomes Associated With Myocardial Injury After Transfemoral and Transapical Transcatheter Aortic Valve Replacement: A Subanalysis From the PARTNER Trial (Placement of Aortic Transcatheter Valves).

OBJECTIVES: This study sought to clarify the clinical and echocardiographic prognostic implication of myocardial injury after transcatheter aortic valve replacement (TAVR). BACKGROUND: The clinical significance of cardiac biomarker elevation after TAVR remains unclear. METHODS: Patients treated with TAVR in the PARTNER (Placement of Aortic Transcatheter Valves) trial were divided into tertiles (T1, T2, T3) based on the difference between the values on post-procedure day 1 and the baseline values of 2 cardiac biomarkers: cardiac troponin I (ΔcTnI); and creatine kinase-myocardial band (ΔCK-MB) fraction. Patients were stratified according to their access route: transfemoral (TF) (n = 1,840) or transapical (TA) (n = 1,173). RESULTS: At 30 days after TF-TAVR, patients in the highest tertile (T3) of cardiac biomarker elevation had a higher rate of all-cause mortality (ΔcTnI: T3: 5.4% vs. T1: 0.5%, p = 0.006; ΔCK-MB: T3: 5.7% vs. T1: 0.9%, p = 0.006) and cardiovascular mortality (ΔcTnI: T3: 4.9% vs. T1: 0.5%, p = 0.01; ΔCK-MB: T3: 3.9% vs. T1: 0.5%, p = 0.02). At 1 year, only patients in the highest CK-MB tertile had higher rates of all-cause (25.4% vs. 16.8%, p = 0.02) and cardiovascular (10.3% vs. 5.0%) mortality. Multivariable analysis demonstrated that greater release of cardiac biomarkers was independently associated with increased mortality in the TF population. After TA-TAVR, being in the highest tertile of cardiac biomarker elevation had no influence on clinical and echocardiographic outcomes at 30 days and 1 year. CONCLUSIONS: After TF-TAVR, a greater degree of myocardial injury was associated with higher rates of 30-day all-cause and cardiovascular mortality. At 1 year, being in the highest tertile of ΔCK-MB was correlated with a higher rate of all-cause and cardiac mortality. Finally, the level of myocardial injury after TA-TAVR had no impact on clinical and echocardiographic outcomes.

Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute Coronary Syndrome.

BACKGROUND: The safety of deferring revascularization based on fractional flow reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the association of FFR and adverse cardiac events among patients with coronary lesions deferred revascularization based on FFR in the setting of ACS versus non-ACS. METHODS AND RESULTS: The study population (674 patients; 816 lesions) was divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when revascularization was deferred based on FFR values >0.80 between October 2002 and July 2010. The association and interaction between FFR and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow-up of 4.5±2.1 years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (DLI), whereas the composite of DLI or myocardial infarction (MI) attributed to a deferred lesion was designated as deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not associated with any increase in adverse cardiac events. In the ACS group, every 0.01 decrease in FFR was associated with a significantly higher rate of cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI (HR, 1.12; 95% CI, 1.06 to 1.18). CONCLUSION: Lower FFR values among ACS patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non-ACS patients.

Prognostic utility of novel biomarkers of cardiovascular stress in patients with aortic stenosis undergoing valve replacement.

OBJECTIVE: In heart failure populations without aortic stenosis (AS), the prognostic utility of multiple biomarkers in addition to clinical factors has been demonstrated. We aimed to determine whether multiple biomarkers of cardiovascular stress are associated with mortality in patients with AS undergoing aortic valve replacement (AVR) independent of clinical factors. METHODS: From a prospective registry of patients with AS, 345 participants who were referred for and treated with AVR (transcatheter (n=183) or surgical (n=162)) were included. Eight biomarkers were measured on blood samples obtained prior to AVR: growth differentiation factor 15 (GDF15), soluble ST2 (sST2), amino-terminal pro-B-type natriuretic peptide (NTproBNP), galectin-3, high-sensitivity cardiac troponin T, myeloperoxidase, high-sensitivity C reactive protein and monocyte chemotactic protein-1. Biomarkers were evaluated based on median value (high vs low) in a Cox proportional hazards model for all-cause mortality and a parsimonious group of biomarkers selected. Mean follow-up was 1.9±1.2 years; 91 patients died. RESULTS: Three biomarkers (GDF15, sST2 and NTproBNP) were retained in the model. One-year mortality was 5%, 12%, 18% and 33% for patients with 0 (n=79), 1 (n=96), 2 (n=87) and 3 (n=83) biomarkers elevated, respectively (p<0.001). After adjustment for the Society of Thoracic Surgeons (STS) risk score, a greater number of elevated biomarkers was associated with increased mortality (referent: 0 elevated): 1 elevated (HR 1.47, 95% CI 0.60 to 3.63, p=0.40), 2 elevated (HR 2.89, 95% CI 1.24 to 6.74, p=0.014) and 3 elevated (HR 4.59, 95% CI 1.97 to 10.71, p<0.001). Among patients at intermediate or high surgical risk (STS score ≥4), 1-year and 2-year mortality rates were 34% and 43% for patients with three biomarkers elevated versus 4% and 4% for patients with 0 biomarkers elevated. When added to the STS score, the number of biomarkers elevated provided a category-free net reclassification improvement of 64% at 1 year (p<0.001). The association between a greater number of elevated biomarkers and increased mortality after valve replacement was similar in the transcatheter and surgical AVR populations. CONCLUSIONS: These findings demonstrate the potential utility of multiple biomarkers to aid in risk stratification of patients with AS. Further studies are needed to evaluate their utility in clinical decision-making in specific AS populations.

Systemic inflammatory response syndrome after transcatheter or surgical aortic valve replacement.

OBJECTIVE: An inflammatory response after cardiac surgery is associated with worse clinical outcomes, but recent trials to attenuate it have been neutral. We evaluated the association between systemic inflammatory response syndrome (SIRS) and mortality after transcatheter (TAVR) and surgical aortic valve replacement (SAVR) for aortic stenosis (AS) and evaluated whether diabetes influenced this relationship. METHODS: Patients (n=747) with severe AS treated with TAVR (n=264) or SAVR (n=483) between January 2008 and December 2013 were included and 37% had diabetes mellitus. SIRS was defined by four criteria 12-48 h after aortic valve replacement (AVR): (1) white blood cell count <4 or >12; (2) heart rate >90; (3) temperature <36 or >38°C; or (4) respiratory rate >20. Severe SIRS was defined as meeting all four criteria. The primary endpoint was 6-month all-cause mortality (60 deaths occurred by 6 months). Inverse probability weighting (IPW) was performed on 44 baseline and procedural variables to minimise confounding. RESULTS: Severe SIRS developed in 6% of TAVR patients and 11% of SAVR patients (p=0.02). Six-month mortality tended to be higher in those with severe SIRS (15.5%) versus those without (7.4%) (p=0.07). After adjustment, severe SIRS was associated with higher 6-month mortality (IPW adjusted HR 2.77, 95% CI 2.04 to 3.76, p<0.001). Moreover, severe SIRS was more strongly associated with increased mortality in diabetic (IPW adjusted HR 4.12, 95% CI 2.69 to 6.31, p<0.001) than non-diabetic patients (IPW adjusted HR 1.74, 95% CI 1.10 to 2.73, p=0.02) (interaction p=0.007). The adverse effect of severe SIRS on mortality was similar after TAVR and SAVR. CONCLUSIONS: Severe SIRS was associated with a higher mortality after SAVR or TAVR. It occurred more commonly after SAVR and had a greater effect on mortality in diabetic patients. These findings may have implications for treatment decisions in patients with AS, may help explain differences in outcomes between different AVR approaches and identify diabetic patients as a high-risk subgroup to target in clinical trials with therapies to attenuate SIRS.

Risk model for estimating the 1-year risk of deferred lesion intervention following deferred revascularization after fractional flow reserve assessment.

AIMS: Although lesions deferred revascularization following fractional flow reserve (FFR) assessment have a low risk of adverse cardiac events, variability in risk for deferred lesion intervention (DLI) has not been previously evaluated. The aim of this study was to develop a prediction model to estimate 1-year risk of DLI for coronary lesions where revascularization was not performed following FFR assessment. METHODS AND RESULTS: A prediction model for DLI was developed from a cohort of 721 patients with 882 coronary lesions where revascularization was deferred based on FFR between 10/2002 and 7/2010. Deferred lesion intervention was defined as any revascularization of a lesion previously deferred following FFR. The final DLI model was developed using stepwise Cox regression and validated using bootstrapping techniques. An algorithm was constructed to predict the 1-year risk of DLI. During a mean (±SD) follow-up period of 4.0 ± 2.3 years, 18% of lesions deferred after FFR underwent DLI; the 1-year incidence of DLI was 5.3%, while the predicted risk of DLI varied from 1 to 40%. The final Cox model included the FFR value, age, current or former smoking, history of coronary artery disease (CAD) or prior percutaneous coronary intervention, multi-vessel CAD, and serum creatinine. The c statistic for the DLI prediction model was 0.66 (95% confidence interval, CI: 0.61-0.70). CONCLUSION: Patients deferred revascularization based on FFR have variation in their risk for DLI. A clinical prediction model consisting of five clinical variables and the FFR value can help predict the risk of DLI in the first year following FFR assessment.