Efficacy and safety of percutaneous patent foramen ovale closure in patients with a hypercoagulable disorder.

BACKGROUND: Transcatheter closure of patent foramen ovale (PFO) in patients with cryptogenic stroke reduces the rate of recurrent events. Although presence of thrombophilia increases the risk for paradoxical emboli through a PFO, such patients were excluded from large randomized trials. OBJECTIVES: We compared the safety and efficacy of percutaneous PFO closure in patients with and without a hypercoagulable state. METHODS: Data from 800 consecutive patients undergoing percutaneous PFO closure in our medical center were analyzed. All patients were independently evaluated by specialists in neurology, cardiology, hematology, and vascular medicine. A post-procedural treatment of at least 3 months of anticoagulation was utilized in patients with thrombophilia. Follow-up events included death, recurrent neurological events, and the need for reintervention for significant residual shunt. RESULTS: A hypercoagulable state was found in 239 patients (29.9%). At median follow-up of 41.9 months, there were no differences in the frequencies of stroke or transient ischemic attack between patients with or without thrombophilia (2.5% in non-hypercoagulable group vs. 3.4% in hypercoagulable group, log-rank test p = 0.35). There were no significant differences in baseline demographics, echocardiographic characteristics, procedural success, or complications between groups. CONCLUSION: Percutaneous PFO closure is a safe and effective therapeutic approach for patients with cryptogenic stroke and an underlying hypercoagulable state.

Residual Shunt After Patent Foramen Ovale Closure and Long-Term Stroke Recurrence: A Prospective Cohort Study.

BACKGROUND: Residual shunt is observed in up to 25% of patients after patent foramen ovale (PFO) closure, but its long-term influence on stroke recurrence currently is unknown. OBJECTIVE: To investigate the association of residual shunt after PFO closure with the incidence of recurrent stroke and transient ischemic attack (TIA). DESIGN: Prospective cohort study comparing stroke or TIA recurrence in patients with and without residual shunt after PFO closure. SETTING: Single hospital center. PARTICIPANTS: 1078 consecutive patients (mean age, 49.3 years) with PFO-attributable cryptogenic stroke who were undergoing percutaneous PFO closure were followed for up to 11 years. MEASUREMENTS: Residual shunt was evaluated by transthoracic echocardiography with saline contrast. Primary outcome was a composite of the first recurrent ischemic stroke or TIA after PFO closure. RESULTS: Compared with complete closure, the presence of residual shunt after PFO closure was associated with an increased incidence of recurrent stroke or TIA: 2.32 versus 0.75 events per 100 patient-years (hazard ratio [HR], 3.05 [95% CI, 1.65 to 5.62]; P < 0.001). This result remained robust after adjustment for important covariates, namely age; study period; device; presence of atrial septal aneurysm, hypertension, hyperlipidemia, diabetes, hypercoagulability, or hypermobile septum; and medication use (HR, 3.01 [CI, 1.59 to 5.69]; P < 0.001). Further stratification based on shunt size revealed that moderate or large residual shunts were associated with a higher risk for stroke or TIA recurrence (HR, 4.50 [CI, 2.20 to 9.20]; P < 0.001); the result for small residual shunts was indeterminate (HR, 2.02 [CI, 0.87 to 4.69]; P = 0.102). LIMITATION: Nonrandomized study with potential unmeasured confounding. CONCLUSION: Among patients undergoing PFO closure to prevent future stroke, the presence of residual shunt, particularly a moderate or large residual shunt, was associated with an increased risk for stroke or TIA recurrence. PRIMARY FUNDING SOURCE: National Institutes of Health.

Impella support and acute kidney injury during high-risk percutaneous coronary intervention: The Global cVAD Renal Protection Study.

BACKGROUND: Protection against acute kidney injury (AKI) has been reported with the use of Impella during high-risk percutaneous coronary intervention (HR-PCI). We sought to evaluate this finding by determining the occurrence of AKI during Impella-supported HR-PCI in patients from the Global cVAD Study and compare this incidence with their calculated AKI risk at baseline. METHODS AND RESULTS: In this prospective, multicenter study, we enrolled 314 consecutive patients. We included 223 patients that underwent nonemergent HR-PCI supported with Impella 2.5 or Impella CP and excluded those requiring hemodialysis prior to HR-PCI (19) and those with insufficient data (72). The primary outcome was AKI postprocedurally at 48 hr versus the predicted risk of AKI according to Mehran risk score. Logistic regression analysis determined predictors of AKI. Overall, 4.9% (11) of Impella-supported patients developed AKI (exclusively stage 1) at 48 hr versus a predicted rate of 21.9%, representing a 77.6% lower AKI rate (p < .0001). In this study, no Impella-supported patients required renal replacement therapy. Estimated glomerular filtration rate (ml/min/1.73 m2 ) alone predicted AKI (adjusted odds ratio [AOR]: 4.915; 95% confidence intervals [CI]: 1.02-23.53, p = .046), and increasing contrast had insignificant effects on AKI during high-risk PCI (AOR: 1.15; 95% CI: 0.87-1.51, p = .332). In patients not protected from AKI, the postprocedure incidence of AKI was not significantly greater and did not correlate with chronic kidney disease severity. CONCLUSION: The incidence of AKI was lower during HR-PCI than expected from current risk models. Although further exploration of this finding is warranted, these data support a new protective strategy against AKI during HR-PCI.

Thirty-day readmissions after transcatheter versus surgical mitral valve repair in high-risk patients with mitral regurgitation: Analysis of the 2014-2015 Nationwide readmissions databases.

OBJECTIVE: Determine the rates, reasons, predictors, and costs of 30-day readmissions following transcatheter mitral valve repair (TMVR) versus surgical mitral valve repair (SMVR) in the United States. BACKGROUND: Data on 30-day readmissions after TMVR are limited. METHODS: High-risk patients with mitral regurgitation (MR) undergoing TMVR or SMVR were identified from the 2014-2015 Nationwide Readmissions Databases. Multivariable stepwise regression models were used to identify independent predictors of 30-day readmission. Risk of 30-day readmission was compared between the two groups using univariate and propensity score adjusted regression models. RESULTS: Among 8,912 patients undergoing mitral valve repair during 2014-2015 (national estimate 17,809), we identified 7,510 (84.7%) that underwent SMVR and 1,402 (15.3%) that underwent TMVR. Thirty-day readmission rates after SMVR and TMVR were 10.7% and 11.7%, respectively (unadjusted OR 1.11, 95% CI 0.89-1.39, p = .35). After propensity score adjustment, TMVR was associated with a lower risk of 30-day readmissions compared with SMVR (adjusted OR 0.70, 95% CI 0.51-0.95, p = .02). Heart failure and arrhythmias were the leading cardiac reasons for readmission. Anemia and fluid and electrolyte disorder were independent predictors of 30-day readmission after TMVR. Demographics, comorbidities, and length of stay were independent predictors of 30-day readmission after SMVR. CONCLUSIONS: One in 10 patients are readmitted within 30 days following TMVR or SMVR. Approximately half of the readmissions are for cardiac reasons. The predictors of 30-day readmission are different among patients undergoing TMVR and SMVR, but can be easily screened for to identify patients at highest risk for readmission.

Impact of left atrial compliance improvement on functional status after percutaneous mitral valvuloplasty.

BACKGROUND: Conventional hemodynamic parameters may not accurately predict symptomatic improvement after percutaneous mitral valvuloplasty (PMV). Changes in left heart chamber compliance following adequate relief o0066 mitral stenosis (MS) may be useful in determining functional capacity after PMV. This study aims to determine the acute effects of PMV on compliance of the left heart and whether its changes relate to the patient's functional capacity. METHODS: One-hundred thirty-seven patients with severe MS undergoing PMV were enrolled. Left atrial (Ca ) and left ventricular (Cv ) compliance were invasively estimated and net atrioventricular compliance (Cav ) was calculated before and immediately after the procedure. B-type natriuretic peptide (BNP) levels were obtained before and 24 hr after the procedure. The primary endpoint was functional status at 6-month follow-up, and the secondary endpoint was a composite of death, mitral valve (MV) replacement, repeat PMV, new onset of atrial fibrillation, or stroke in patients in whom PMV was successful. RESULTS: The mean age was 43 ± 12 years, and 119 patients were female (87%). After PMV, Ca and Cav improved significantly from 5.3 [IQR 3.2-8.2] mL/mmHg to 8.7 [5.3-19.2] mL/mmHg (P < 0.001) and 2.2 [1.6-3.4] to 2.8 [2.1-4.1] mL/mmHg (P < 0.001), respectively, whereas Cv did not change (4.6 [3.2-6.8] to 4.4 [3.1-5.6]; P = 0.637). Plasma BNP levels significantly decreased after PMV, with no correlation between its variation and changes in left chamber compliance. At 6-month follow-up, NYHA functional class remained unchanged in 32 patients (23%). By multivariable analyses, changes in Ca immediately after PMV (adjusted OR 1.42; 95% CI 95% 1.02 to 1.97; P = 0.037) and younger age (adjusted OR 0.95; CI 95% 0.92-0.98; P = 0.004), predicted improvement in functional capacity at 6-month follow-up, independent of postprocedural data. The secondary endpoint were predicted by post-PMV mean gradient (adjusted HR 1.363; 95% CI 95% 1.027-1.809; P = 0.032), and lack of functional improvement at 6-month follow-up (adjusted HR 4.959; 95% 1.708-14.403; P = 0.003). CONCLUSIONS: Ca and Cav increase significantly after PMV with no change in Cv . The improvement of Ca is an important predictor of functional status at 6-month follow up, independently of other hemodynamic data. Postprocedural mean gradient and lack of short-term symptomatic improvement were predictors of adverse outcome.

Association between Public Reporting of Outcomes and the Use of Mechanical Circulatory Support in Patients with Cardiogenic Shock.

Risk-averse behavior has been reported among physicians and facilities treating cardiogenic shock in states with public reporting. Our objective was to evaluate if public reporting leads to a lower use of mechanical circulatory support in cardiogenic shock. We conducted a retrospective study with the use of the National Inpatient Sample from 2005 to 2011. Hospitalizations of patients ≥18 years old with a diagnosis of cardiogenic shock were included. A regional comparison was performed to identify differences between reporting and nonreporting states. The main outcome of interest was the use of mechanical circulatory support. A total of 13043 hospitalizations for cardiogenic shock were identified of which 9664 occurred in reporting and 3379 in nonreporting states (age 69.9 ± 0.4 years, 56.8% men). Use of mechanical circulatory support was 32.8% in this high-risk population. Odds of receiving mechanical circulatory support were lower (OR 0.50; 95% CI 0.43-0.57; p < 0.01) and in-hospital mortality higher (OR 1.19; 95% CI 1.06-1.34; p < 0.01) in reporting states. Use of mechanical circulatory support was also lower in the subgroup of patients with acute myocardial infarction and cardiogenic shock in reporting states (OR 0.61; 95% CI 0.51-0.72; p < 0.01). In conclusion, patients with cardiogenic shock in reporting states are less likely to receive mechanical circulatory support than patients in nonreporting states.

Cholesterol embolization syndrome: An under-recognized entity in cardiovascular interventions.

Cholesterol embolization syndrome (CES) is a multi-systemic disease caused by embolization of atherosclerotic plaque contents from proximal large-caliber artery to distal small to medium arteries, occurring spontaneously or more commonly after vascular intervention. This report is a comprehensive review of the reported cases of CES found in our literature search. We discuss the risk factors, clinical manifestations, management, and prognosis of CES. The major predisposing factors for CES include older age, male sex, atherosclerotic cardiovascular risk factors, anticoagulation, and femoral access route. The composite incidence of atheroembolic renal disease was 92% and mortality 63%. Our review highlights the importance to recognize this disease entity for the cardiologist and nephrologist.

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.

Coronary revascularization for acute myocardial infarction in the HIV population.

OBJECTIVE: To analyze trends in management and outcomes of patients infected with the human immunodeficiency virus (HIV) undergoing percutaneous coronary intervention (PCI) for an acute myocardial infarction (AMI) in the United States. BACKGROUND: Infection with HIV is an independent risk factor for accelerated atherosclerosis associated with higher rates of AMI. Current trends and outcomes of HIV-infected individuals presenting with AMI in the United States remain unknown. METHODS: Using the Healthcare Cost and Utilization Project National Inpatient Sample database we identified HIV-infected individuals who underwent PCI for an AMI from 2002 to 2013. Multivariable logistic regression and propensity-score matching were performed to analyze outcomes. RESULTS: We identified a total of 59 194 patients of which 7841 underwent PCI during index hospitalization (13.3%). Most patients were men (71%), ≥50 years of age (82%), and white (74%). ST-elevation myocardial infarction was present in 21% of cases. Charlson comorbidity index (CCI) was 5.67 ± 0.4. Predictors of post-procedural complications included female sex, black race, higher CCI, and placement of a bare metal stent, whereas predictors of mortality included occurrence of a complication, ST-elevation myocardial infarction, age ≥70 years, and higher CCI. Conversely, placement of a drug-eluting stent was associated with a reduced risk of complications and mortality. After propensity-score matching, HIV-infected individuals were less likely to undergo PCI and receive a drug-eluting stent, while having longer length of stay, higher hospitalization costs, and higher in-hospital mortality when compared to non-infected individuals. CONCLUSION: Significant disparities continue to affect HIV-infected individuals undergoing PCI for AMI in the United States.

The echo score revisited: Impact of incorporating commissural morphology and leaflet displacement to the prediction of outcome for patients undergoing percutaneous mitral valvuloplasty.

BACKGROUND: Current echocardiographic scoring systems for percutaneous mitral valvuloplasty (PMV) have limitations. This study examined new, more quantitative methods for assessing valvular involvement and the combination of parameters that best predicts immediate and long-term outcome after PMV. METHODS AND RESULTS: Two cohorts (derivation n=204 and validation n=121) of patients with symptomatic mitral stenosis undergoing PMV were studied. Mitral valve morphology was assessed by using both the conventional Wilkins qualitative parameters and novel quantitative parameters, including the ratio between the commissural areas and the maximal excursion of the leaflets from the annulus in diastole. Independent predictors of outcome were assigned a points value proportional to their regression coefficients: mitral valve area ≤1 cm(2) (2), maximum leaflets displacement ≤12 mm (3), commissural area ratio ≥1.25 (3), and subvalvular involvement (3). Three risk groups were defined: low (score of 0-3), intermediate (score of 5), and high (score of 6-11) with observed suboptimal PMV results of 16.9%, 56.3%, and 73.8%, respectively. The use of the same scoring system in the validation cohort yielded suboptimal PMV results of 11.8%, 72.7%, and 87.5% in the low-, intermediate-, and high-risk groups, respectively. The model improved risk classification in comparison with the Wilkins score (net reclassification improvement 45.2%; P<0.0001). Long-term outcome was predicted by age and postprocedural variables, including mitral regurgitation, mean gradient, and pulmonary pressure. CONCLUSIONS: A scoring system incorporating new quantitative echocardiographic parameters more accurately predicts outcome following PMV than existing models. Long-term post-PMV event-free survival was predicted by age, degree of mitral regurgitation, and postprocedural hemodynamic data.

Percutaneous left ventricular assist device for high-risk percutaneous coronary interventions: Real-world versus clinical trial experience.

BACKGROUND: High-risk percutaneous coronary intervention (PCI) supported by percutaneous left ventricular assist devices offers a treatment option for patients with severe symptoms, complex and extensive coronary artery disease, and multiple comorbidities. The extrapolation from clinical trial to real-world practice has inherent uncertainties. We compared the characteristics, procedures, and outcomes of high-risk PCI supported by a microaxial pump (Impella 2.5) in a multicenter registry versus the randomized PROTECT II trial (NCT00562016). METHODS: The USpella registry is an observational multicenter voluntary registry of Impella technology. A total of 637 patients treated between June 2007 and September 2013 were included. Of them, 339 patients would have met enrollment criteria for the PROTECT II trial. These were compared with 216 patients treated in the Impella arm of PROTECT II. RESULTS: Compared to the clinical trial, registry patients were older (70 ± 11.5 vs 67.5 ± 11.0 years); more likely to have chronic kidney disease (30% vs 22.7%), prior myocardial infarction (69.3% vs 56.5%), or prior bypass surgery (39.4% vs. 30.2%); and had similar prevalence of diabetes, peripheral vascular disease, and prior stroke. Registry patients had more extensive coronary artery disease (2.2 vs 1.8 diseased vessels) and had a similar Society of Thoracic Surgeons predicted risk of mortality. At hospital discharge, registry patients experienced a similar reduction in New York Heart Association class III to IV symptoms compared to trial patients. Registry patients had a trend toward lower in-hospital mortality (2.7% vs 4.6, P = .27). CONCLUSIONS: USpella provides a real-world and contemporary estimation of the type of procedures and outcomes of high-risk patients undergoing PCI supported by Impella 2.5. Despite the higher risk of registry patients, clinical outcomes appeared to be favorable and consistent compared with the randomized trial.

Proteomic signatures of serum albumin-bound proteins from stroke patients with and without endovascular closure of PFO are significantly different and suggest a novel mechanism for cholesterol efflux.

BACKGROUND: The anatomy of PFO suggests that it can allow thrombi and potentially harmful circulatory factors to travel directly from the venous to the arterial circulation - altering circulatory phenotype. Our previous publication using high-resolution LC-MS/MS to profile protein and peptide expression patterns in plasma showed that albumin was relatively increased in donor samples from PFO-related than other types of ischemic strokes. Since albumin binds a host of molecules and acts as a carrier for lipoproteins, small molecules and drugs, we decided to investigate the albumin-bound proteins (in a similar sample cohort) in an effort to unravel biological changes and potentially discover biomarkers related to PFO-related stroke and PFO endovascular closure. METHODS: The method used in this study combined albumin immuno-enrichment with high resolution LC-MS in order to specifically capture and quantify the albumin-bound proteins. Subsequently, we measured cholesterol and HDL in a larger, separate cohort of PFO stroke patients, pre and post closure. RESULTS: The results demonstrated that a number of proteins were specifically associated with albumin in samples with and without endovascular closure of the PFO, and that the protein profiles were very different. Eight proteins, typically associated with HDL were common to both sample sets and quantitatively differently abundant. Pathway analysis of the MS results suggested that enhanced cholesterol efflux and reduced lipid oxidation were associated with PFO closure. Measurement of total cholesterol and HDL in a larger cohort of PFO closure samples using a colorimetric assay was consistent with the proteomic predictions. CONCLUSIONS: The collective data presented in this study demonstrate that analysis of albumin-bound proteins could provide a valuable tool for biomarker discovery on the effects of PFO endovascular closure. In addition, the results suggest that PFO endovascular closure can potentially have effects on HDL, cholesterol and albumin-bound ApoA-I abundance, therefore possibly providing benefits in cardioprotective functions.

Influence of hospital volume on outcomes of percutaneous atrial septal defect and patent foramen ovale closure: a 10-years US perspective.

BACKGROUND: Contemporary data regarding percutaneous closure of atrial septal defect/patent foramen ovale (ASD/PFO) are lacking. We evaluated the current trends in utilization of ASD/PFO closure in adults and investigated the effect of annual hospital volume on in-hospital outcomes. METHODS: We queried the Nationwide Inpatient Sample between the years 2001 and 2010 using the International Classification of Diseases (ICD-9-CM) procedure code for percutaneous closure of ASD/PFO with device. Hierarchical mixed effects models were generated to identify the independent multivariate predictors of outcomes. RESULTS: A total of 7,107 percutaneous ASD/PFO closure procedures (weighted n = 34,992) were available for analysis. A 4.7-fold increase in the utilization of this procedure from 3/million in 2001 to 14/million adults in 2010 in US (P < 0.001) was noted. Overall, percutaneous ASD/PFO closure was associated with 0.5% mortality and 12% in-hospital complications. The utilization of intracardiac echocardiography (ICE) increased 15 fold (P < 0.001) during the study period. The procedures performed at the high volume hospitals [2nd (14-37 procedures/year) and 3rd (>38 procedures/year) tertile] were associated with significant reduction in complications, length of stay and cost of hospitalization when compared to those performed at lowest volume centers (<13 procedures/year). Majority (70.5%) of the studied hospitals were found to be performing <10 procedures/year hence deviating from the ACC/AHA/SCAI clinical competency guidelines. CONCLUSIONS: Low hospital volume is associated with an increased composite (mortality and procedural complications) adverse outcome following ASD/PFO closure. In the interest of patient safety, implementation of the current guidelines for minimum required annual hospital volume to improve clinical outcomes is warranted.

Incidence and Predictors of Pacemaker Implantation in Patients Undergoing Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with symptomatic aortic stenosis who are at high risk for surgical aortic valve replacement. The development of conduction abnormalities is a major complication in the postprocedural period of TAVR. OBJECTIVES: The objective of this study was to investigate the development of postprocedural conduction abnormalities and the requirement of permanent pacemaker (PPM) implantation in patients undergoing TAVR. METHODS: Data from 137 consecutive patients who underwent TAVR (Edwards SAPIEN valve, Edwards Lifesciences, Irvine, CA, USA) between June 2008 and October 2012 were reviewed. Patients with prior history of PPM (n = 27) were excluded. The role of various predictors for pacemaker implantation after TAVR, including the valve index (calculated as [valve size/left ventricular outflow tract diameter] × 100) was investigated. RESULTS: A total of 31/110 (28.2%) patients required implantation of a PPM after TAVR. The median time to implantation of a PPM was 5 days after the procedure. The development of postprocedural complete heart block was the most common indication for implantation of a PPM (16/31; 51.6%). On multivariate analysis, the presence of preexisting right bundle branch block (RBBB) was found to be a strong predictor of PPM implantation after TAVR (adjusted odds ratio: 4.87; 95% confidence interval: 1.29-18.46, P = 0.020). Using the receiver operated curve analysis, a cut-off value of valve index of 128 was found to be a strong predictor for PPM implantation with a sensitivity of 73% and specificity of 61% (c statistic = 0.68). CONCLUSIONS: This study identified the presence of prior RBBB and a valve index of 128 as important risk factors for PPM implantation after TAVR. A larger implanted valve size relative to left ventricular outflow tract diameter leads to a greater compression of the intrinsic conduction system, increasing the need for pacemaker placement.

Evaluating the learning curve in the prospective Randomized Clinical Trial of hemodynamic support with Impella 2.5 versus Intra-Aortic Balloon Pump in patients undergoing high-risk percutaneous coronary intervention: a prespecified subanalysis of the PROTECT II study.

BACKGROUND: The introduction of new medical devices may be accompanied by a learning curve. METHODS: To evaluate the impact of the device learning curve on the outcomes of PROTECT II trial, comparing Impella 2.5 versus the intra-aortic balloon pump (IABP) during high-risk percutaneous coronary intervention, we report on a prespecified analysis, excluding the first Impella 2.5 and IABP patients at each site. RESULTS: A total of 448 patients were enrolled at 74 sites. Among these, 58 patients were the first to receive Impella 2.5 at their site, 62 were the first to receive IABP. A trend toward higher major adverse events (MAEs) at 30 days was observed for the subgroup of first versus remaining Impella 2.5 patients: 44.8% versus 31.7%, P = .072. MAE rates for the first and remaining IABP patients were similar at 30 days. After exclusion of the first patient in each group, MAE rates for Impella 2.5 and IABP were 31.7% versus 40.0% (P = .119) at 30 days and 38.0% versus 50.0% (P = .029) at 90 days. CONCLUSIONS: Significantly lower 90-day MAE rates were observed with the use of Impella 2.5 compared to the use of IABP after excluding the first patient per group at each site. This prespecified analysis suggests a learning curve associated with initial introduction of the Impella 2.5. Clinical trials should better address the training aspect of new devices, especially when compared with more established devices.

Left ventricular end-diastolic pressure as an independent predictor of outcome during balloon aortic valvuloplasty.

OBJECTIVES: In this study, we examined the predictive value of the left ventricular end-diastolic pressure (LVEDP) in patients undergoing balloon aortic valvuloplasty (BAV). BACKGROUND: The LVEDP is a useful indicator of hemodynamic status in patients with severe aortic stenosis. In BAV, decompensated heart failure is associated with worse outcomes. METHODS: We identified all consecutive patients with severe symptomatic aortic stenosis who underwent retrograde BAV at the Massachusetts General Hospital from 2004 to 2008. Patients were stratified and compared according to their baseline LVEDP into ≤15 mm Hg, 16-20 mm Hg, 21-25 mm Hg, and ≥26 mm Hg. Procedural and in-hospital outcomes and adverse events were compared. Multivariate logistic regression was used for the adjusted analysis. RESULTS: A total of 111 patients with a mean age of 83±11 years underwent BAV. Of these, the LVEDP was ≤15 mm Hg in 29 (26%), 16-20 mm Hg in 41 (37%), 21-25 mm Hg in 16 (14%), and ≥26 mm Hg in 25 (23%) patients. Baseline characteristics were similar among the four groups. Noticeably, patients with high LVEDP levels had significantly higher rates of the combined endpoint of in-hospital death, myocardial infarction (MI), cardiopulmonary arrest, and tamponade was P = 0.02. Periprocedural MI was more common among those with higher LVEDP (16% vs. 2.3%; P = 0.04). Multivariate analysis revealed LVEDP (OR 1.08, for each mm Hg increase in pressure, 95 % CI 1.02-1.14), small LV chamber size, and New York Heart Association class as independent predictors of adverse outcomes. CONCLUSIONS: The LVEDP is an important independent predictor of poor in-hospital outcome during BAV. In these patients, the immediate hemodynamic status may be more important than the baseline left ventricular systolic function. Hemodynamic optimization before or during BAV should be considered and may be beneficial.

Optimizing rotational atherectomy in high-risk percutaneous coronary interventions: insights from the PROTECT ΙΙ study.

OBJECTIVE: To study rotational atherectomy (RA) outcomes in patients undergoing high-risk PCI randomized to receive hemodynamic support using either IABP or Impella 2.5 in the PROTECT II trial. BACKGROUND: RA of heavily calcified lesions is often necessary for complex PCI but can be associated with slow-flow, hypotension, and higher risk of periprocedural MI. METHODS: We compared baseline, angiographic, procedural characteristics, and outcomes of patients treated with and without RA. We examined also RA technique and outcomes. RESULTS: RA was used in 52 of 448 patients (32 with Impella vs 20 with IABP, P = 0.08). RA patients were older (72 vs. 67 yo, P = 0.0009), more likely to have prior CABG (48 vs. 32%, P = 0.017), higher STS (8.1 vs. 5.7, P = 0.012) and higher SYNTAX scores (37 vs. 29, P < 0.0001). At 90 days, RA use was associated with higher incidence of MI but no mortality difference. RA was used more aggressively with Impella resulting in higher rate of periprocedural MI (P < 0.01), with no difference in mortality between groups (P = 0.78). Repeat revascularization occurred less frequently with Impella (P < 0.001). There were no differences in 90-day major adverse events between IABP and Impella in patients undergoing RA (P = 0.29). In patients not treated with RA, fewer MAEs were observed with Impella compared with IABP (P = 0.03). CONCLUSIONS: Patients who were treated with RA had more comorbidities, and more complex and extensive coronary artery disease. In patients with Impella, more aggressive RA use resulted in fewer revascularization events but higher incidence of periprocedural MI.

A combined epidemiologic and metabolomic approach improves CKD prediction.

Metabolomic approaches have begun to catalog the metabolic disturbances that accompany CKD, but whether metabolite alterations can predict future CKD is unknown. We performed liquid chromatography/mass spectrometry-based metabolite profiling on plasma from 1434 participants in the Framingham Heart Study (FHS) who did not have CKD at baseline. During the following 8 years, 123 individuals developed CKD, defined by an estimated GFR of <60 ml/min per 1.73 m(2). Numerous metabolites were associated with incident CKD, including 16 that achieved the Bonferroni-adjusted significance threshold of P≤0.00023. To explore how the human kidney modulates these metabolites, we profiled arterial and renal venous plasma from nine individuals. Nine metabolites that predicted CKD in the FHS cohort decreased more than creatinine across the renal circulation, suggesting that they may reflect non-GFR-dependent functions, such as renal metabolism and secretion. Urine isotope dilution studies identified citrulline and choline as markers of renal metabolism and kynurenic acid as a marker of renal secretion. In turn, these analytes remained associated with incident CKD in the FHS cohort, even after adjustment for eGFR, age, sex, diabetes, hypertension, and proteinuria at baseline. Addition of a multimarker metabolite panel to clinical variables significantly increased the c-statistic (0.77-0.83, P<0.0001); net reclassification improvement was 0.78 (95% confidence interval, 0.60 to 0.95; P<0.0001). Thus, the addition of metabolite profiling to clinical data may significantly improve the ability to predict whether an individual will develop CKD by identifying predictors of renal risk that are independent of estimated GFR.