Initial experience with the fourth generation MitraClip™: Outcomes, procedural aspects, and considerations for device selection.

OBJECTIVES: We present our initial experience with the fourth-generation MitraClip™ (G4) system and propose preliminary criteria for device selection. BACKGROUND: The MitraClip™ G4 system recently underwent a "controlled release" for transcatheter edge-to-edge mitral valve repair. The four new devices include technical improvements such as controlled gripper actuation (independent leaflet capture) and continuous left atrial pressure monitoring. To date, a patient-specific device selection algorithm, and the technology's impact on procedural times and success, have not been described. METHODS: We present an initial multi-center experience and short-term outcomes with the new system, suggest procedural and imaging considerations, and propose initial guidance for device selection. RESULTS: Sixty-one procedures performed by three operators at two centers between November 2019 and May 2020 were analyzed. At 30-day follow-up, there were three deaths (4.9%), four neurological events (6.6%), and seven re-hospitalizations (11.5%). Fifty-nine patients achieved device and procedural success (96.7%), and there was one device-related technical issue (1.6%). Compared to the same operators utilizing the third generation MitraClip™, the G4 system resulted in a significant reduction in the median number of clips used per patient (1 IQR 1-2 vs. 2 IQR 1-3, p = .023) and a trend toward shorter device times. CONCLUSION: Based on our initial experience, we found that the MitraClip™ G4 system is associated with high procedural success and fewer devices needed per procedure. The expanded device options may allow a more targeted approach to the myriad of pathologic presentations of mitral regurgitation. This early experience should provide a foundational opportunity for further refinement.

Heterogeneity of Treatment Effects in an Analysis of Pooled Individual Patient Data From Randomized Trials of Device Closure of Patent Foramen Ovale After Stroke.

Importance: Patent foramen ovale (PFO)-associated strokes comprise approximately 10% of ischemic strokes in adults aged 18 to 60 years. While device closure decreases stroke recurrence risk overall, the best treatment for any individual is often unclear. Objective: To evaluate heterogeneity of treatment effect of PFO closure on stroke recurrence based on previously developed scoring systems. Design, Setting, and Participants: Investigators for the Systematic, Collaborative, PFO Closure Evaluation (SCOPE) Consortium pooled individual patient data from all 6 randomized clinical trials that compared PFO closure plus medical therapy vs medical therapy alone in patients with PFO-associated stroke, and included a total of 3740 participants. The trials were conducted worldwide from 2000 to 2017. Exposures: PFO closure plus medical therapy vs medical therapy alone. Subgroup analyses used the Risk of Paradoxical Embolism (RoPE) Score (a 10-point scoring system in which higher scores reflect younger age and the absence of vascular risk factors) and the PFO-Associated Stroke Causal Likelihood (PASCAL) Classification System, which combines the RoPE Score with high-risk PFO features (either an atrial septal aneurysm or a large-sized shunt) to classify patients into 3 categories of causal relatedness: unlikely, possible, and probable. Main Outcomes and Measures: Ischemic stroke. Results: Over a median follow-up of 57 months (IQR, 24-64), 121 outcomes occurred in 3740 patients. The annualized incidence of stroke with medical therapy was 1.09% (95% CI, 0.88%-1.36%) and with device closure was 0.47% (95% CI, 0.35%-0.65%) (adjusted hazard ratio [HR], 0.41 [95% CI, 0.28-0.60]). The subgroup analyses showed statistically significant interaction effects. Patients with low vs high RoPE Score had HRs of 0.61 (95% CI, 0.37-1.00) and 0.21 (95% CI, 0.11-0.42), respectively (P for interaction = .02). Patients classified as unlikely, possible, and probable using the PASCAL Classification System had HRs of 1.14 (95% CI, 0.53-2.46), 0.38 (95% CI, 0.22-0.65), and 0.10 (95% CI, 0.03-0.35), respectively (P for interaction = .003). The 2-year absolute risk reduction was -0.7% (95% CI, -4.0% to 2.6%), 2.1% (95% CI, 0.6%-3.6%), and 2.1% (95% CI, 0.9%-3.4%) in the unlikely, possible, and probable PASCAL categories, respectively. Device-associated adverse events were generally higher among patients classified as unlikely; the absolute risk increases in atrial fibrillation beyond day 45 after randomization with a device were 4.41% (95% CI, 1.02% to 7.80%), 1.53% (95% CI, 0.33% to 2.72%), and 0.65% (95% CI, -0.41% to 1.71%) in the unlikely, possible, and probable PASCAL categories, respectively. Conclusions and Relevance: Among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO. Application of this classification system has the potential to guide individualized decision-making.

Risk of Paradoxical Embolism (RoPE)-Estimated Attributable Fraction Correlates With the Benefit of Patent Foramen Ovale Closure: An Analysis of 3 Trials.

BACKGROUND AND PURPOSE: In patients with cryptogenic stroke and patent foramen ovale (PFO), the Risk of Paradoxical Embolism (RoPE) Score has been proposed as a method to estimate a patient-specific "PFO-attributable fraction"-the probability that a documented PFO is causally-related to the stroke, rather than an incidental finding. The objective of this research is to examine the relationship between this RoPE-estimated PFO-attributable fraction and the effect of closure in 3 randomized trials. METHODS: We pooled data from the CLOSURE-I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack due to Presumed Paradoxical Embolism through a Patent Foramen Ovale), RESPECT (Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment), and PC (Clinical Trial Comparing Percutaneous Closure of Patent Foramen Ovale [PFO] Using the Amplatzer PFO Occluder With Medical Treatment in Patients With Cryptogenic Embolism) trials. We examine the treatment effect of closure in high RoPE score (≥7) versus low RoPE score (<7) patients. We also estimated the relative risk reduction associated with PFO closure across each level of the RoPE score using Cox proportional hazard analysis. We estimated a patient-specific attributable fraction using a PC trial-compatible (9-point) RoPE equation (omitting the neuroradiology variable), as well as a 2-trial analysis using the original (10-point) RoPE equation. We examined the Pearson correlation between the estimated attributable fraction and the relative risk reduction across RoPE strata. RESULTS: In the low RoPE score group (<7, n=912), the rate of recurrent strokes per 100 person-years was 1.37 in the device arm versus 1.68 in the medical arm (hazard ratio, 0.82 [0.42-1.59] P=0.56) compared with 0.30 versus 1.03 (hazard ratio, 0.31 [0.11-0.85] P=0.02) in the high RoPE score group (≥7, n=1221); treatment-by-RoPE score group interaction, P=0.12. The RoPE score estimated attributable fraction anticipated the relative risk reduction across all levels of the RoPE score, in both the 3-trial (r=0.95, P<0.001) and 2-trial (r=0.92, P<0.001) analyses. CONCLUSIONS: The RoPE score estimated attributable fraction is highly correlated to the relative risk reduction of device versus medical therapy. This observation suggests the RoPE score identifies patients with cryptogenic stroke who are likely to have a PFO that is pathogenic rather than incidental.

Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke.

BACKGROUND: Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown. METHODS: In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization. The results of the analysis of the primary outcome from the original trial period have been reported previously; the current analysis of data from the extended follow-up period was considered to be exploratory. RESULTS: We enrolled 980 patients (mean age, 45.9 years) at 69 sites. Patients were followed for a median of 5.9 years. Treatment exposure in the two groups was unequal (3141 patient-years in the PFO closure group vs. 2669 patient-years in the medical-therapy group), owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat population, recurrent ischemic stroke occurred in 18 patients in the PFO closure group and in 28 patients in the medical-therapy group, resulting in rates of 0.58 events per 100 patient-years and 1.07 events per 100 patient-years, respectively (hazard ratio with PFO closure vs. medical therapy, 0.55; 95% confidence interval [CI], 0.31 to 0.999; P=0.046 by the log-rank test). Recurrent ischemic stroke of undetermined cause occurred in 10 patients in the PFO closure group and in 23 patients in the medical-therapy group (hazard ratio, 0.38; 95% CI, 0.18 to 0.79; P=0.007). Venous thromboembolism (which comprised events of pulmonary embolism and deep-vein thrombosis) was more common in the PFO closure group than in the medical-therapy group. CONCLUSIONS: Among adults who had had a cryptogenic ischemic stroke, closure of a PFO was associated with a lower rate of recurrent ischemic strokes than medical therapy alone during extended follow-up. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270 .).

Validation of scoring system predicting permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is being increasingly performed in patients with severe aortic stenosis. Despite newer generation valves, atrioventricular (AV) conduction disturbance is a common complication, necessitating permanent pacemaker (PPM) implantation in about 10% of patients. Hence, it is imperative to improve periprocedural risk stratification to predict PPM implantation after TAVR. The objective of this study was to externally validate a novel risk-stratification model derived from the National Inpatient Sample (NIS) database that predicts risk of PPM from TAVR. METHODS: Components of the score included pre-TAVR left and right bundle branch block, sinus bradycardia, second-degree AV block, and transfemoral approach. The scoring system was applied to 917 patients undergoing TAVR at our institution from November 2011 to February 2017. We assessed its predictive accuracy by looking at two components: discrimination using the C-statistic and calibration using the Hosmer-Lemeshow goodness of fit test. RESULTS: Ninety patients (9.8%) required PPM. The scoring system showed good discrimination with C-statistic score of 0.6743 (95% CI: 0.618-0.729). Higher scores suggested increased PPM risk, that is, 7.3% with score ⩽3, 19.23% with score 4-6, and 37.50% with score ≥7. Patients requiring PPM were older (81.4 versus 78.7 years, P = .002). Length of stay and in-hospital mortality was significantly higher in PPM group. CONCLUSIONS: The NIS database derived PPM risk prediction model was successfully validated in our database with acceptable discriminative and gradation capacity. It is a simple but valuable tool for patient counseling pre-TAVR and in identifying high-risk patients.

Rates, predictors, and outcomes of early readmissions after tricuspid valve surgery.

BACKGROUND: The data on readmissions following tricuspid valve repair/replacement (TVR) are scarce. We examined rates, predictors, causes, and outcomes of readmissions after TVR, using the National Readmission Database. METHODS: The International Classification of Diseases-9th version was used to identify the patients who underwent isolated TVR or concomitant aortic, mitral, and coronary bypass surgeries. Rates, causes, and outcomes were assessed using the analysis of variance and the χ2 test, and predictors of readmissions were evaluated using multivariate analysis. RESULTS: A total of 8254 patients who underwent TVR during 2013 to 2014 were included, of whom 1994 (24.16%) were isolated, and 6260 (75.84%) were performed concomitantly with other heart valve or coronary bypass surgery. A total of 1720 (20.84%) patients were readmitted within 30 days. The readmission rates were 448 (22.46%) after isolated TVR and similar after concomitant TVR (TVR + aortic valve replacement, TVR + mitral valve repair, TVR + coronary artery bypass graft, and TVR + multiple) (P = .194); whereas 1305 (20.11%) and 414 (23.45%) were after tricuspid valve repair and replacement (P = .080), respectively. The independent predictors of readmission were acute kidney injury during index visit and Charlson comorbidity index of more than 2. Mean time to readmission and median length of stay during readmission were 13.02 (±7.93) and 5 (interquartile range: 3-9) days, respectively. Total mortality during rehospitalization was 105 (6.1%), a very high (26.86%) number of patients were discharged to skilled facilities after readmission. CONCLUSIONS: One out of five patients were readmitted within 30 days after the TVR, associated with 6.1% mortality during rehospitalization, and very high need for skilled facility placement.

New-onset left bundle branch block after transcatheter aortic valve replacement is associated with adverse long-term clinical outcomes in intermediate-risk patients: an analysis from the PARTNER II trial.

AIMS: Transcatheter aortic valve replacement (TAVR) is now an established therapy for intermediate-risk surgical candidates with symptomatic, severe aortic stenosis. The clinical impact of new-onset left bundle branch block (LBBB) after TAVR remains controversial and has not been studied in intermediate-risk patients. We therefore sought to analyse outcomes associated with new LBBB in a large cohort of intermediate-risk patients treated with TAVR. METHODS AND RESULTS: A total of 2043 patients underwent TAVR in the PARTNER II trial and S3 intermediate-risk registry and survived to hospital discharge. Patients were excluded from the current analysis due to baseline conduction disturbances, pre-existing permanent pacemaker (PPM), and new PPM during the index hospitalization. Clinical outcomes at 2 years were compared between patients with and without persistent, new-onset LBBB at hospital discharge, and multivariable analysis was performed to identify predictors of mortality. Among 1179 intermediate-risk patients, new-onset LBBB at discharge occurred in 179 patients (15.2%). Patients with new LBBB were similar to those without except for more frequent diabetes and more frequent treatment with SAPIEN 3 vs. SAPIEN XT. At 2 years, new LBBB was associated with increased rates of all-cause mortality (19.3% vs. 10.8%, P = 0.002), cardiovascular mortality (16.2% vs. 6.5%, P < 0.001), rehospitalization, and new PPM implantation. By multivariable analysis, new LBBB remained an independent predictor of 2-year all-cause [hazard ratio (HR) 1.98, 95% confidence interval (95% CI) 1.33, 2.96; P < 0.001] and cardiovascular (HR 2.66 95% CI 1.67, 4.24; P < 0.001) mortality. New LBBB was also associated with worse left ventricular systolic function at 1 and 2-year follow-up. CONCLUSIONS: In a large cohort of intermediate-risk patients from the PARTNER II trial and registry, persistent, new-onset LBBB occurred in 15.2% of patients without baseline conduction disturbances or pacemaker. New LBBB was associated with adverse clinical outcomes at 2 years, including all-cause and cardiovascular mortality, rehospitalization, new pacemaker implantation, and worsened left ventricular systolic function. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov #NCT01314313 and NCT03222128.

Outcomes of transcatheter mitral valve replacement for degenerated bioprostheses, failed annuloplasty rings, and mitral annular calcification.

Aims: We sought to evaluate the outcomes of transcatheter mitral valve replacement (TMVR) for patients with degenerated bioprostheses [valve-in-valve (ViV)], failed annuloplasty rings [valve-in-ring (ViR)], and severe mitral annular calcification [valve-in-mitral annular calcification (ViMAC)]. Methods and results: From the TMVR multicentre registry, procedural and clinical outcomes of ViV, ViR, and ViMAC were compared according to Mitral Valve Academic Research Consortium (MVARC) criteria. A total of 521 patients with mean Society of Thoracic Surgeons score of 9.0 ± 7.0% underwent TMVR (322 patients with ViV, 141 with ViR, and 58 with ViMAC). Trans-septal access and the Sapien valves were used in 39.5% and 90.0%, respectively. Overall technical success was excellent at 87.1%. However, left ventricular outflow tract obstruction occurred more frequently after ViMAC compared with ViR and ViV (39.7% vs. 5.0% vs. 2.2%; P < 0.001), whereas second valve implantation was more frequent in ViR compared with ViMAC and ViV (12.1% vs. 5.2% vs. 2.5%; P < 0.001). Accordingly, technical success rate was higher after ViV compared with ViR and ViMAC (94.4% vs. 80.9% vs. 62.1%; P < 0.001). Compared with ViMAC and ViV groups, ViR group had more frequent post-procedural mitral regurgitation ≥moderate (18.4% vs. 13.8% vs. 5.6%; P < 0.001) and subsequent paravalvular leak closure (7.8% vs. 0.0% vs. 2.2%; P = 0.006). All-cause mortality was higher after ViMAC compared with ViR and ViV at 30 days (34.5% vs. 9.9% vs. 6.2%; log-rank P < 0.001) and 1 year (62.8% vs. 30.6% vs. 14.0%; log-rank P < 0.001). On multivariable analysis, patients with failed annuloplasty rings and severe MAC were at increased risk of mortality after TMVR [ViR vs. ViV, hazard ratio (HR) 1.99, 95% confidence interval (CI) 1.27-3.12; P = 0.003; ViMAC vs. ViV, HR 5.29, 95% CI 3.29-8.51; P < 0.001]. Conclusion: The TMVR provided excellent outcomes for patients with degenerated bioprostheses despite high surgical risk. However, ViR and ViMAC were associated with higher rates of adverse events and mid-term mortality compared with ViV.

An update on the management and outcomes of cancer patients with severe aortic stenosis.

OBJECTIVES: We compared the outcomes of aortic valve replacement (AVR) by transcatheter (TAVR) and surgical (SAVR) routes with those of optimal medical management in patients with cancer and severe aortic stenosis (AS). BACKGROUND: Cancer therapy requires optimal cardiac output; however, the treatment of AS in cancer patients is not established. METHODS: Cancer patients with severe AS during January 2009 through February 2018 at a large cancer center were identified. Demographic and clinical characteristics including previous or active cancer diagnosis, history of chest radiotherapy, AS treatment, and survival were collected. Univariate Cox proportional hazards regression, the Kaplan-Meier analysis, and log-rank tests were used to compare overall survival (OS) between AS treatment groups. RESULTS: Sixty-five cancer patients with severe AS were identified; 28 received optimal medical treatment alone, 30 received TAVR, and seven received SAVR. The patients were predominantly male (n = 44, 68%) with a mean age of 71.17 years. The median OS was 9.87 months, and the most common cause of death was cancer (n = 29, 94% of deaths). AVR was associated with a lower risk of death than no AVR (hazard ratio [HR] 0.38, P = 0.007), and patients who underwent TAVR (HR 0.36, P = 0.01) had better survival than those with no AVR. Malignancy type, stage, and treatment were not associated with OS. CONCLUSIONS: Patients with cancer and severe AS who underwent AVR, predominantly TAVR, experienced better survival than those who had no AVR regardless of cancer type or cancer treatment. TAVR may be considered in patients with cancer and AS.

Outcomes and readmissions after transcatheter and surgical aortic valve replacement in patients with cirrhosis: A propensity matched analysis.

BACKGROUND: The data on the comparative outcomes and readmissions after transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in patients with cirrhosis are limited. We compared mortality, complications, discharge disposition, 30-day readmission rates, length of stay, and cost of hospitalization in cirrhotic patients undergoing TAVR and SAVR. METHODS: The National Inpatient Sample (NIS) and the National Readmission Database (NRD) were used for the study. The International Classification of Diseases-9th version was used to define cohorts of patients undergoing TAVR and SAVR. Patients undergoing concomitant other valve or coronary bypass surgery were excluded. Propensity-score matching was used to compare the outcomes between the groups. RESULTS: From 2012 to 2014, a total of 126 and 157 patients with cirrhosis underwent TAVR and SAVR, respectively. Of the 283 patients, 16 (5.7%) died during the same hospitalization. We found 345 patients with cirrhosis who had undergone an aortic valve replacement (156 with TAVR, and 189 with SAVR) in the 2013 and 2014 NRD. On propensity matching, there were no significant differences between the in-hospital mortality, readmissions, hospitalization costs, and discharges to home within the TAVR and SAVR groups. However, post-procedure length of stay (6.3 vs. 10.2 days; P < 0.001) and blood transfusion rates (22% vs. 58%; P < 0.001) were significantly lower in TAVR patients. CONCLUSIONS: Cirrhotic patients undergoing TAVR has high, but similar mortality and 30-day readmission rates when compared to SAVR; however, has shorter length of stay and lower blood transfusion rates.

Early readmissions after transcatheter and surgical aortic valve replacement.

OBJECTIVES: We aimed to determine and compare the prevalence, and predictors of readmissions after the transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). BACKGROUND: There are limited data on the readmission rates after TAVR in comparison with SAVR. METHODS: We analyzed the data from 2013 National Readmission Database. Propensity-matched pairs were used to analyze differences in readmission rates between TAVR and SAVR for patients aged ≥65. RESULTS: A total of 24,020 (TAVR-transfemoral 3,469, TAVR-transapical 1,433, SAVR 19,118) patients were included. The readmission rates were not statistically different for all propensity-matched TAVR and SAVR patients (17.2% vs. 20.6%, P = 0.28). However, in subgroup analysis, transapical TAVR had the highest readmission rate (22.8% vs. 16.5% vs. 16.0%, P < 0.001, respectively) and readmission leading to death (7.1% vs. 5.3% vs. 3.9%, P = 0.022, respectively) when compared with transfemoral TAVR and SAVR. In all the groups, two-thirds of readmissions were due to noncardiac causes. Congestive heart failure (CHF) and arrhythmia were the most frequent cardiac etiologies. The independent predictors of readmission were female sex, CHF, and chronic obstructive pulmonary disease. Patients who received care in teaching hospitals had lower probability of readmission. CONCLUSIONS: One of six patients were readmitted within 30 days after the aortic valve replacement. On propensity score analysis, there were no significant differences between the early readmission rates between TAVR and SAVR groups. However, the patients undergoing transapical TAVR were at higher risk for readmission, and subsequent deaths when compared with transfemoral TAVR and SAVR. © 2017 Wiley Periodicals, Inc.

Closure of patent foramen ovale versus medical therapy after cryptogenic stroke.

BACKGROUND: Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age. METHODS: In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated. RESULTS: We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased. CONCLUSIONS: In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the prespecified per-protocol and as-treated analyses, with a low rate of associated risks. (Funded by St. Jude Medical; RESPECT ClinicalTrials.gov number, NCT00465270.).

Clinical characteristics and outcomes after unplanned intraaortic balloon counterpulsation in the Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction trial.

BACKGROUND: Despite advances in primary percutaneous coronary intervention (pPCI) and regional systems of care, the development of cardiogenic shock is associated with poor clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). We sought to better characterize the baseline characteristics and clinical outcomes of patients who underwent crossover to intraaortic balloon counterpulsation (IABC) in the CRISP AMI trial. METHODS: Patients with anterior STEMI were randomized to IABC before pPCI or pPCI alone. Infarct size and 6-month clinical outcomes were evaluated in patients both in the pPCI-alone group who did undergo crossover to IABC and those who did not undergo crossover to IABC. RESULTS: Among 176 patients randomized to pPCI alone, 161 patients did not later receive IABC during the index hospitalization, and 15 patients (8.5%) underwent crossover and did receive unplanned IABC. Hypotension and/or cardiogenic shock precipitated crossover to IABC in 12 patients (80%). Patients who underwent crossover to IABC demonstrated lower systolic and diastolic blood pressures on admission. At 6 months, rates of death (26.7% vs 3.1%, P = .003), readmission for severe hypotension (53.3% vs 3.7%, P < .001), resuscitated cardiac arrest, and ventricular arrhythmia were higher in the group that did crossover to IABC. Crossover to IABC was not associated with increased infarct size. CONCLUSIONS: The most significant predictor of crossover to IABC in the setting of anterior STEMI was relative hypotension at the time of hospital admission, and crossover to IABC in CRISP AMI was associated with significantly worse clinical outcomes.

Comparison of 30-day mortality and myocardial scar indices for patients treated with prehospital reduced dose fibrinolytic followed by percutaneous coronary intervention versus percutaneous coronary intervention alone for treatment of ST-elevation myocardial infarction.

OBJECTIVES: We investigated whether prehospital, reduced dose fibrinolysis coupled with urgent percutaneous coronary intervention (FAST-PCI) reduces mortality and cardiac magnetic resonance (CMR) measures of infarct size, compared with primary percutaneous coronary intervention (PPCI), in patients with ST-elevation myocardial infarction (STEMI). BACKGROUND: Current standard therapy for STEMI is PPCI. However, FAST-PCI may shorten ischemic time (IT) and improve outcomes. METHODS: Eligible STEMI patients received prehospital, reduced dose fibrinolysis along with standard therapy, and were transported for urgent percutaneous coronary intervention, or else they received usual treatment without prehospital fibrinolysis. Patients were divided retrospectively into four groups based on IT (<120, 120-179, 180-239 min, ≥240) for a mortality analysis cohort, and into three groups (<120, 120-179, ≥180 min) for a CMR analysis cohort. Within each IT group, patients were compared by FAST-PCI vs. PPCI strategy. RESULTS: Between 1/2007 and 2/2014, 1,112 STEMI patients were treated. FAST-PCI was employed in 551 and PPCI in 561. Of these, 357 (32.1%) underwent CMR. The treatment groups were well matched. In STEMI patients with short IT (<120 and 120-179 min groups), those treated by FAST-PCI had lower 30-day mortality and myocardial scar sizes compared with PPCI treatment. For IT ≥180 min, the mortalities and myocardial scar sizes were equivalent for both groups. CONCLUSIONS: In STEMI patients with IT <180 min, FAST-PCI may reduce 30-day mortality and myocardial scar size compared with PPCI. This suggests that infarct interventions must be instituted within 3 hr of symptom onset in order to detect an optimal beneficial effect both clinically and by CMR measurement. © 2016 Wiley Periodicals, Inc.

Ischemic time is a better predictor than door-to-balloon time for mortality and infarct size in ST-elevation myocardial infarction.

BACKGROUND: Current guidelines for ST-elevation myocardial infarction (STEMI) recommend early revascularization with optimal ischemic time (IT) < 120 min and door-to-balloon (D2B) time < 90 min. The focus of most studies has been D2B time, while IT is not frequently reported. We tested the hypothesis that total IT is a better predictor than D2B time for mortality and infarct size. METHODS AND RESULTS: Between December 2008 and April 2013, 786 patients with STEMI were treated in our STEMI center, and 262 of these had cardiac magnetic resonance imaging 3-5 days after the index event. Total IT was defined as time from symptom onset to device activation, while D2B time was defined as hospital arrival to device activation. Patients were divided into three groups according to IT (<120, 120-239, ≥240 min) and into four groups according to D2B time (<30, 30-59, 60-89, ≥90 min). Baseline demographics including age, cardiac risk factors, and LAD infarct location were similar between groups. The 30-day mortality rate significantly increased across IT groups but did not correlate with D2B time groups. Similarly, infarct size significantly increased across IT groups but did not correlate with D2B time groups. CONCLUSIONS: In STEMI patients, IT was a better predictor than D2B time for 30-day mortality and infarct size. Our findings suggest that the focus of STEMI care should be directed at early initiation of therapy and minimizing IT rather than on D2B time alone. The potential impact of IT reporting in current STEMI registries merits further consideration. © 2015 Wiley Periodicals, Inc.

Safety and efficacy of coil embolization of the septal perforator for septal ablation in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVE: The objective of this study was to evaluate safety, efficacy, and durability of coil embolization of the major septal perforator of the left anterior descending coronary artery in patients with hypertrophic obstructive cardiomyopathy (HOCM). BACKGROUND: The long-term effect of coil embolization therapy in HOCM patients is not well defined. METHODS: We evaluated 24 symptomatic HOCM patients in a single center who underwent coil embolization of the septal perforator artery(ies). RESULTS: Twenty-four patients on optimal medical therapy presented with NYHA functional class III (75%) or IV (25%) underwent the procedure. The procedure was successful in 22 patients, with significant reduction in left ventricular outflow tract (LVOT) gradient. The functional class significantly improved to class I (54.2%) or II (41.7%) (P < = 0.01). The LVOT gradient was significantly lower during follow up echocardiography (21.3 ± 19 vs. 81.3 ± 41 mm Hg; P < = 0.01). Interventricular septal thickness decreased over time (16.3 ± 3 vs. 18.5 ± 2 mm, P< = 0.01). The procedure was aborted in one of the patients after the third coil prolapsed from the septal perforator in to the left anterior descending artery. The coil was effectively snared out. Three patients required additional coil placement in the second major septal perforator. New permanent pacemaker placement was required in one patient. However, three patients underwent ICD implantation at follow up due to ventricular arrhythmias. CONCLUSIONS: The results of this study suggest that the use of coil embolization for septal ablation is safe, effective, and durable in patients with symptomatic HOCM. © 2016 Wiley Periodicals, Inc.

Percutaneous repair or surgery for mitral regurgitation.

BACKGROUND: Mitral-valve repair can be accomplished with an investigational procedure that involves the percutaneous implantation of a clip that grasps and approximates the edges of the mitral leaflets at the origin of the regurgitant jet. METHODS: We randomly assigned 279 patients with moderately severe or severe (grade 3+ or 4+) mitral regurgitation in a 2:1 ratio to undergo either percutaneous repair or conventional surgery for repair or replacement of the mitral valve. The primary composite end point for efficacy was freedom from death, from surgery for mitral-valve dysfunction, and from grade 3+ or 4+ mitral regurgitation at 12 months. The primary safety end point was a composite of major adverse events within 30 days. RESULTS: At 12 months, the rates of the primary end point for efficacy were 55% in the percutaneous-repair group and 73% in the surgery group (P=0.007). The respective rates of the components of the primary end point were as follows: death, 6% in each group; surgery for mitral-valve dysfunction, 20% versus 2%; and grade 3+ or 4+ mitral regurgitation, 21% versus 20%. Major adverse events occurred in 15% of patients in the percutaneous-repair group and 48% of patients in the surgery group at 30 days (P<0.001). At 12 months, both groups had improved left ventricular size, New York Heart Association functional class, and quality-of-life measures, as compared with baseline. CONCLUSIONS: Although percutaneous repair was less effective at reducing mitral regurgitation than conventional surgery, the procedure was associated with superior safety and similar improvements in clinical outcomes. (Funded by Abbott Vascular; EVEREST II ClinicalTrials.gov number, NCT00209274.).

Patent Foramen Ovale Closure in Older Patients With Stroke: Patient Selection for Trial Feasibility.

BACKGROUND AND OBJECTIVES: Whether patent foramen ovale (PFO) closure benefits older patients with PFO and cryptogenic stroke is unknown because randomized controlled trials (RCTs) have predominantly enrolled patients younger than 60 years of age. Our objective was to estimate anticipated effects of PFO closure in older patients to predict the numbers needed to plan an RCT. METHODS: Effectiveness estimates are derived from major observational studies (Risk of Paradoxical Embolism [RoPE] Study and Oxford Vascular Study, together referred to as the "RoPE-Ox" database) and all 6 major RCTs (Systematic, Collaborative, PFO Closure Evaluation [SCOPE] Consortium). To estimate stroke recurrence risk, observed outcomes were calculated for patients older than 60 years in the age-inclusive observational databases (n = 549). To estimate the reduction in the rate of recurrent stroke associated with PFO closure vs medical therapy based on the RoPE score and the presence of high-risk PFO features, a Cox proportional hazards regression model was developed on the RCT data in the SCOPE database (n = 3,740). These estimates were used to calculate sample sizes required for a future RCT. RESULTS: Five-year risk of stroke recurrence using Kaplan-Meier estimates was 13.7 (95% CI 10.5-17.9) overall, 14.9% (95% CI 10.2-21.6) in those with high-risk PFO features. Predicted relative reduction in the event rate with PFO closure was 12.9% overall, 48.8% in those with a high-risk PFO feature. Using these estimates, enrolling all older patients with cryptogenic stroke and PFO would require much larger samples than those used for prior PFO closure trials, but selectively enrolling patients with high-risk PFO features would require totals of 630 patients for 90% power and 471 patients for 80% power, with an average of 5 years of follow-up. DISCUSSION: Based on our projections, anticipated effect sizes in older patients with high-risk features make a trial in these subjects feasible. With lengthening life expectancy in almost all regions of the world, the utility of PFO closure in older adults is increasingly important to explore.

Endothelin-1 release during the early phase of reperfusion is a mediator of myocardial reperfusion injury.

PURPOSE: In acute myocardial infarction, left ventricular (LV) unloading reduces endothelin-1 (ET-1) release. We tested that endogenous ET-1 released during acute myocardial infarction might mediate ischemia/reperfusion (I/R) injury by stimulating increased intracellular calcium concentration, [Ca(2+)]i, and apoptosis. METHODS: Rabbits were subjected to 1 h of coronary artery occlusion followed by 3 h of reperfusion. Unloading was initiated 15 min prior to reperfusion and was maintained during reperfusion. The control group was subjected to reperfusion. Animals were treated with ET-1 receptor antagonist BQ123. In parallel, isolated rabbit cardiomyocytes subjected to simulated I/R with or without ET-1 or BQ123, intracellular Ca(2+) and cell death were assessed with flow cytometry. RESULTS: LV unloading prior to reperfusion reduced myocardial ET-1 release at 2 h of reperfusion. Infarct size was reduced in unloaded and BQ123 groups versus controls. LV unloading and BQ123 treatment reduced the percentage of apoptotic cells associated with increases in Bcl-2 protein levels in ischemic regions. BQ123 reduced both ET-1-induced [Ca(2+)]i increase and cell death for myocytes subjected to stimulated I/R. CONCLUSION: We propose that components of reperfusion injury involve ET-1 release which stimulates calcium overload and apoptosis. Intravenous ET-1 receptor blockade prior to reperfusion may be a protective adjunct to reperfusion therapy in acute myocardial infarction patients.