Recurrent Stent Thrombosis Following Myocardial Infarction Associated With VITT-Like Antibodies.

Early stent thrombosis is a rare complication of percutaneous intervention and is associated with significant 30-day mortality. We present a novel case of multiple recurrent early stent thrombosis consistent with spontaneous vaccine-induced thrombotic thrombocytopenia. We were successfully able to manage this unusual condition through an interdisciplinary collaboration.

CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention in Diverse Clinical Settings.

Background Studies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss-of-function (LOF) variant carriers versus non-carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real-world outcomes with the clinical implementation of CYP2C19-guided antiplatelet therapy after PCI. Methods and Results Data from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative therapy with prasugrel or ticagrelor was recommended for patients with a CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or hospitalization for unstable angina) within 12 months following PCI. Moderate or severe/life-threatening bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative therapy versus clopidogrel (adjusted HR, 0.56; 95% CI 0.39-0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71-1.60). There was no difference in bleeding with alternative therapy versus clopidogrel in either LOF carriers or those without a LOF allele. Conclusions Real-world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those without a LOF allele treated with clopidogrel or alternative therapy. These data suggest that PCI patients treated with clopidogrel should undergo genotyping so that CYP2C19 LOF carriers can be identified and treated with alternative therapy.

Management of Patients With Giant Cell Myocarditis: JACC Review Topic of the Week.

Giant cell myocarditis is a rare, often rapidly progressive and potentially fatal, disease due to T-cell lymphocyte-mediated inflammation of the myocardium that typically affects young and middle-aged adults. Frequently, the disease course is marked by acute heart failure, cardiogenic shock, intractable ventricular arrhythmias, and/or heart block. Diagnosis is often difficult due to its varied clinical presentation and overlap with other cardiovascular conditions. Although cardiac biomarkers and multimodality imaging are often used as initial diagnostic tests, endomyocardial biopsy is required for definitive diagnosis. Combination immunosuppressive therapy, along with guideline-directed medical therapy, has led to a paradigm shift in the management of giant cell myocarditis resulting in an improvement in overall and transplant-free survival. Early diagnosis and prompt management can decrease the risk of transplantation or death, which remain common in patients who present with cardiogenic shock.

Transseptal Puncture Learning Curve for Transcatheter Edge-to-Edge Mitral Valve Repair.

OBJECTIVE: This study examined the learning curve for transseptal puncture (TSP) during transcatheter edge-to-edge mitral valve repair (TEER) performed by a dedicated mitral valve structural heart team. Effective TSP is mandatory for TEER but can be time-consuming and associated with complications including pericardial effusion and cardiac tamponade. METHODS: TSP was performed on 107 consecutive patients (76 ± 1 years, 52% male) undergoing TEER between 2014 and 2019. TSP was performed by each structural heart team member (1 cardiologist, 2 cardiac surgeons) on a rotating case-by-case basis. No team member had prior independent TSP experience. Data collected included total procedure time, TSP time (time elapsed between procedure start and septal crossing), and number of TSP attempts before successful puncture. Cumulative sum (CUSUM) of deviations from the mean across sequential cases were used to examine learning curves. RESULTS: Median total procedure time was 107 min, and the median TSP time was 14 min. Greater case number was significantly associated with both lower TSP time (r s = -0.22, P = 0.022) and lower total procedure time (r s = -0.29, P = 0.003). The majority of patients required only 1 TSP attempt (79%). There was a significant quadratic relationship between case number and the CUSUM for TSP time, with the learning curve peaking at 49 cases. CONCLUSIONS: TSP for TEER has a substantial learning curve, requiring >50 cases to achieve acceptable efficiency. Even once proficiency is demonstrated, TSP remains a time-consuming component of TEER. Improvements in transseptal access technology may significantly decrease the time needed to master TSP and may improve the safety and precision of the procedure.

Development of a Reproducible Swine Model of Chronic Ischemic Mitral Regurgitation: Lessons Learned.

BACKGROUND: Durability of mitral valve repair for ischemic mitral regurgitation (IMR) remains poor. We established a swine model of chronic IMR, and describe the methods and lessons learned from this model. METHODS: Thirty-five swine underwent percutaneous myocardial infarction with ethanol ablation of the circumflex or obtuse marginal (OM) arteries. Swine were followed with routine echocardiography for the development of severe IMR. Once severe IMR was established, swine underwent mitral valve operations on cardiopulmonary bypass. After operation, swine were survived up to 7 weeks. Angiographic and echocardiographic features of swine who developed severe IMR (IMR swine) and those who did not (non-IMR swine) were compared. RESULTS: The median number of OM arteries was 3, with 2 OM arteries infarcted. Acute survival after the myocardial infarction was 74% (26 of 35) with 3 (9%) early, postoperative deaths. Among the 23 swine with follow-up to determine IMR status, 14 of 23 (61%) developed significant IMR. Among IMR pigs, left ventricular (LV) ejection fraction decreased from 65% pre-myocardial infarction to 45% pre-mitral valve intervention (P < .001). Among non-IMR swine, LV ejection fraction decreased nonsignificantly from baseline (60%) to latest follow-up (55%) (P = .443). LV end-diastolic dimension (P = .039), wall motion score (P = .027), global circumferential strain (P = .014), and global longitudinal strain (P = .023) were significantly worse in IMR compared with non-IMR swine. CONCLUSIONS: A reproducible percutaneous model of severe IMR in swine is feasible with a guided anesthetic and perioperative approach. This model can serve as a platform to better understand the mechanism of IMR and subsequently to test novel repair techniques.

Multisite Investigation of Strategies for the Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy.

CYP2C19 genotype-guided antiplatelet therapy following percutaneous coronary intervention is increasingly implemented in clinical practice. However, challenges such as selecting a testing platform, communicating test results, building clinical decision support processes, providing patient and provider education, and integrating methods to support the translation of emerging evidence to clinical practice are barriers to broad adoption. In this report, we compare and contrast implementation strategies of 12 early adopters, describing solutions to common problems and initial performance metrics for each program. Key differences between programs included the test result turnaround time and timing of therapy changes, which are both related to the CYP2C19 testing model and platform used. Sites reported the need for new informatics infrastructure, expert clinicians such as pharmacists to interpret results, physician champions, and ongoing education. Consensus lessons learned are presented to provide a path forward for those seeking to implement similar clinical pharmacogenomics programs within their institutions.

Hybrid Coronary Revascularization for the Treatment of Multivessel Coronary Artery Disease: A Multicenter Observational Study.

BACKGROUND: Hybrid coronary revascularization (HCR) combines minimally invasive surgical coronary artery bypass grafting of the left anterior descending artery with percutaneous coronary intervention (PCI) of non-left anterior descending vessels. HCR is increasingly used to treat multivessel coronary artery disease that includes stenoses in the proximal left anterior descending artery and at least 1 other vessel, but its effectiveness has not been rigorously evaluated. OBJECTIVES: This National Institutes of Health-funded, multicenter, observational study was conducted to explore the characteristics and outcomes of patients undergoing clinically indicated HCR and multivessel PCI for hybrid-eligible coronary artery disease, to inform the design of a confirmatory comparative effectiveness trial. METHODS: Over 18 months, 200 HCR and 98 multivessel PCI patients were enrolled at 11 sites. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE) (i.e., death, stroke, myocardial infarction, repeat revascularization) within 12 months post-intervention. Cox proportional hazards models were used to model time to first MACCE event. Propensity scores were used to balance the groups. RESULTS: Mean age was 64.2 ± 11.5 years, 25.5% of patients were female, 38.6% were diabetic, and 4.7% had previous stroke. Thirty-eight percent had 3-vessel coronary artery disease, and the mean SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score was 19.7 ± 9.6. Adjusted for baseline risk, MACCE rates were similar between groups within 12 months post-intervention (hazard ratio [HR]: 1.063; p = 0.80) and during a median 17.6 months of follow-up (HR: 0.868; p = 0.53). CONCLUSIONS: These observational data from this first multicenter study of HCR suggest that there is no significant difference in MACCE rates over 12 months between patients treated with multivessel PCI or HCR, an emerging modality. A randomized trial with long-term outcomes is needed to definitively compare the effectiveness of these 2 revascularization strategies. (Hybrid Revascularization Observational Study; NCT01121263).

Intracoronary Stem Cell Delivery to the Right Ventricle: A Preclinical Study.

Clinical protocols for stem cell-based therapies are currently under development for patients with hypoplastic left heart syndrome. An ideal cell delivery method should have minimal safety risks and provide a wide distribution of cells to the nonischemic right ventricle (RV). However, the optimal strategy for stem cell delivery to the RV has yet to be explored in a preclinical model, necessary for a hypoplastic left heart syndrome trial. Human c-kit+ cardiac stem cells (CSCs) were delivered to healthy Yorkshire swine through the proximal right coronary artery with a stop and reflow technique. The effect of premedication with antiarrhythmic (AA) medications in this model was retrospectively reviewed, with the primary outcome of survival 2 hours after infusion. A group underwent CSC delivery to the RV without prophylactic AA medication (no AA, n = 7), whereas the second group was premedicated with a loading dose and intravenous infusion of amiodarone and lidocaine (AA, n = 13). Cardiac biopsies were obtained from each chamber to ascertain the biodistribution of CSCs. Survival was significantly greater in the prophylactic AA group compared with the group without AA (13/13 [100%] vs 1/7 [14.3%], P < 0.0001). Cardiac arrest during balloon inflation was the cause of death in each of the nonmedicated animals. In the premedicated group, 9 (69.2%) pigs experienced transient ST segment changes in the precordial leads during CSC delivery, which resolved spontaneously. Most c-kit+ CSCs were distributed to lateral segments of the RV free wall, consistent with the anatomical course of the right coronary artery (lateral RV, 19.2 ± 1.5 CSCs/field of view vs medial RV, 10.4 ± 1.3 CSCs/field of view, P < 0.0001). Few c-kit+ CSCs were identified in the right atrium, septum, or left ventricle. Prophylactic infusion of AA enhances survival in swine undergoing intracoronary delivery of human c-kit+ CSCs to the RV. Additionally, intracoronary delivery results in a limited biodistribution of c-kit+ CSCs within the RV. Human clinical protocols can be optimized by requiring infusion of AA medications before cell delivery.

Advanced hybrid closed chest revascularization: an innovative strategy for the treatment of multivessel coronary artery disease†.

OBJECTIVES: Conventional hybrid revascularization (CHR) combines minimally invasive placement of an internal mammary artery graft to the anterior wall and percutaneous coronary intervention (PCI) of non-anterior wall targets. In this study we assess perioperative and midterm outcomes of advanced hybrid revascularization (AHR) defined as the combination of single or multivessel (MV) totally endoscopic coronary artery bypass grafting (TECAB) with single or multivessel PCI. METHODS: In total, 90 AHR patients [median age 62 years (35-86)] were compared with 90 CHR patients [median age 60 years (35-85)] in terms of perioperative and mid-term outcomes. The outcomes of the three different AHR options (MV-TECAB + PCI, MV-PCI + TECAB, MV-TECAB + MV-PCI) as well as the sequence of the interventions were further compared. Risk factors for major adverse cardiac and cerebral events (MACCEs) related to the hybrid revascularization strategy were calculated. RESULTS: No perioperative deaths occurred either in the AHR group or in the CHR group, rates of myocardial infarction (3.3% vs 3.3%, P = 0.196) were similar between CHR and AHR. Operative times were longer in the AHR group [337 (137-794) min vs 272 (148-550) min, P = 0.002] and conversion rates slightly higher (P = 0.060); however, intensive care unit length of stay (P = 0.162) and hospital length of stay (P = 0.238) were similar. There was no difference in the follow-up survival (P = 0.091), freedom from angina (P = 0.844), PCI target vessel revascularization (P = 0.563), TECAB target vessel revascularization (P = 0.135) and MACCEs (P = 0.601) between CHR and AHR at follow-up. No differences were detected between the three variations of AHR in perioperative outcome, mid-term survival, freedom from MACCEs and reintervention. Neither the number nor type of TECAB/PCI targets, nor the sequence of interventions were significant predictors for MACCEs at follow-up. CONCLUSIONS: AHR yields comparable results with CHR and can be taken into consideration as a sternum-sparing technique for the treatment of MV-coronary artery disease in selected patients.

Implementation of pharmacogenetics: the University of Maryland Personalized Anti-platelet Pharmacogenetics Program.

Despite a substantial evidence base, implementation of pharmacogenetics into routine patient care has been slow due to a number of non-trivial practical barriers. We implemented a Personalized Anti-platelet Pharmacogenetics Program (PAP3) for cardiac catheterization patients at the University of Maryland Medical Center and the Baltimore Veterans Administration Medical Center Patients' are offered CYP2C19 genetic testing, which is performed in our Clinical Laboratory Improvement Amendment (CLIA)-certified Translational Genomics Laboratory. Results are returned within 5 hr along with clinical decision support that includes interpretation of results and prescribing recommendations for anti-platelet therapy based on the Clinical Pharmacogenetics Implementation Consortium guidelines. Now with a working template for PAP3, implementation of other drug-gene pairs is in process. Lessons learned as described in this article may prove useful to other medical centers as they implement pharmacogenetics into patient care, a critical step in the pathway to personalized and genomic medicine.

Predictors and consequences of postoperative atrial fibrillation following robotic totally endoscopic coronary bypass surgery.

OBJECTIVES: Postoperative atrial fibrillation (AFib) is common in patients undergoing coronary artery bypass grafting. Little information is available concerning AFib following minimally invasive cardiac surgery. The aim of our study was to assess the incidence of AFib after totally endoscopic coronary artery bypass (TECAB) grafting and to investigate the factors influencing its occurrence. METHODS: Between 2001 and 2010, we performed TECAB in 384 patients, 73% male, aged 60 (37-90) years. Single-vessel bypasses were performed in 280 patients, and 104 received multivessel coronary revascularization. Procedures were performed on the beating heart in 80 cases, and 164 patients underwent a hybrid intervention. RESULTS: A total of 59 patients (15.4%) developed AFib after TECAB. Univariate analysis showed hypertension (P=0.005), increased age (P=0.007), body weight (P=0.006), body mass index (P=0.005), EuroSCORE (P=0.035) and total TECAB operation time (P=0.01) to be significantly associated with AFib. We also found an increased incidence of AFib in patients undergoing hybrid interventions (P=0.036) and beating heart TECAB (P=0.003). Age (P<0.001) and higher body weight (P=0.003) were the only predictors found to be significant in multivariate analysis. Hospital mortality was 1.7% (1 of 59) in the group of patients with AFib and 0.6% (2 of 325) in the group that showed no AFib after operation (P=n.s.). Hospital stay was 7 (4-54) days in patients with AFib and 6 (2-33) days in those without AFib (P=n.s.). There was no significant 5-year survival difference in patients with and without postoperative AFib (94 vs 94%, P=n.s.). CONCLUSIONS: We conclude that the incidence of postoperative AFib in TECAB is relatively low. Age and body weight are the most important predictors of postoperative AFib following TECAB. Short-term clinical outcome and intermediate-term survival are similar in patients with and without postoperative AFib.

Robotically assisted hybrid coronary revascularization: does sequence of intervention matter?

OBJECTIVE: Hybrid coronary revascularization (HCR) is a treatment strategy for the revascularization of multivessel coronary disease that combines the advantages of both minimally invasive surgical techniques and percutaneous coronary intervention (PCI). The optimal sequence by which revascularization should be accomplished has not been determined. We investigated clinical outcomes in a series of patients planned for HCR via robotically assisted totally endoscopic coronary artery bypass (TECAB) and standard PCI based on revascularization sequence. METHODS: A total of 238 patients planned for HCR between 2001 and 2011 were divided into three groups based on treatment sequence: (a) TECAB before PCI, (b) PCI before TECAB, and (c) same-session procedure. Multiple procedural and clinical end points before discharge and up to 2 years after the procedure were compared between the three groups in an intention-to-treat analysis. Demographic features were reviewed to determine baseline differences between each group. RESULTS: Of the 238 patients, 175 (73.5%) underwent TECAB before PCI, 38 patients (16.0%) underwent PCI before TECAB, and 25 (10.5%) underwent a simultaneous revascularization procedure. At baseline, the patients undergoing TECAB before PCI were significantly older. There was a significantly higher incidence of previous myocardial infarction in the PCI-first group (P < 0.001). There was a significant difference in intensive care unit (ICU) length of stay (LOS), with shorter ICU stays in the simultaneous revascularization group (P = 0.031) and shorter hospital LOS in the PCI before TECAB group (P = 0.021). CONCLUSIONS: In conclusion, revascularization sequence did not dramatically impact clinical outcomes in our observational study. The patients undergoing PCI-first and same-session interventions had shorter hospital and ICU LOS compared with the patients undergoing surgery first. Our findings suggest that no revascularization approach is arbitrarily superior and that revascularization sequence should be individualized on the basis of patient presentation and anatomical considerations.

Five hundred cases of robotic totally endoscopic coronary artery bypass grafting: predictors of success and safety.

BACKGROUND: Robotic technology has enabled totally endoscopic coronary artery bypass (TECAB) grafting. Little information is available on factors associated with successful and safe performance of TECAB. We report a 10-year multicenter experience with 500 cases, elucidating on predictors of success and safety in TECAB procedures. METHODS: Between 2001 and 2011, 500 patients (364 [73%] men; 136 [27%] women; median age [minimum-maximum] 60 years [31-90 years], median EuroSCORE 2 [0-13]), underwent TECAB. Single, double, triple, and quadruple TECAB was performed in 334, 150, 15, and 1 patient, respectively. Univariate analysis and binary regression models were used to identify predictors of success and safety. Success was defined as freedom from any adverse event and conversion procedure, safety was defined as freedom from major adverse cardiac and cerebral events, major vascular injury, and long-term ventilation. RESULTS: Success and safety rates were 80% (400 cases) and 95% (474 cases), respectively. Intraoperative conversions to larger thoracic incisions were required in 49 (10%) patients. The median operative time was 305 minutes (112-1,050 minutes), and the mean lengths of stay in the intensive unit (ICU) and in hospital were 23 hours (11-1,048 hours) and 6 days (2-4 days), respectively. Independent predictors of success were single-vessel TECAB (p = 0.004), arrested-heart (AH)-TECAB (p = 0.027), non-learning curve case (p = 0.049), and transthoracic assistance (p = 0.035). The only independent predictor of safety was EuroSCORE (p = 0.002). CONCLUSIONS: Single-vessel and multivessel TECAB procedures can be safely performed with good reproducible results. Predictors of success include procedure simplicity and non-learning curve cases, whereas predictors of safety are mainly associated with patient selection.

Acute coronary syndromes: from the emergency department to the cardiac care unit.

Acute coronary syndromes result in a significant burden of morbidity and mortality in the United States. This spectrum of acute coronary thrombosis (including unstable angina, non-ST-segment elevation myocardial infarction, and ST-elevation myocardial infarction) has been well studied in large clinical trials. This review details the initial management of patients presenting with possible acute coronary syndromes in the context of care from the emergency department to the cardiac care unit. The importance of a rapid and focused evaluation, risk stratification, and appropriate therapies are discussed.

Hybrid coronary revascularization using robotic totally endoscopic surgery: perioperative outcomes and 5-year results.

BACKGROUND: Hybrid coronary revascularization combines minimally invasive coronary artery bypass grafting and catheter-based interventions. This treatment option represents a viable alternative to both open multivessel coronary bypass surgery through sternotomy and multivessel percutaneous coronary intervention. The surgical component of hybrid coronary intervention can be offered in a completely endoscopic fashion using robotic technology. We report on one of the largest series to date. METHODS: From 2001 to 2011, 226 patients (age, 61 years [range, 31 to 90 years]; 77.0% male; EuroSCORE, 2 [range, 0 to 13]) underwent hybrid coronary interventions on an intention-to-treat basis. Robotically assisted procedures were performed using the daVinci, daVinci S, and daVinci Si surgical telemanipulation systems (Intuitive Surgical, Inc, Sunnyvale, CA) and included 147 single, 72 double, and 7 triple endoscopic coronary artery bypass grafting procedures. Surgery was carried out first in 160 cases (70.8%), percutaneous coronary intervention was carried out first in 38 cases (16.8%), and 28 patients underwent simultaneous operations in a hybrid operating room (12.4%). Drug-eluting stents were used in 70.0% of the patients. RESULTS: Hospital mortality was 3 of 226 patients (1.3%), and hospital stay averaged 6 days (range, 3 to 54 days). Patients walked outside 7 days (range, 3 to 97 days) postoperatively and performed general household work 14 days (range, 7 to 180 days) postoperatively. Full activity was resumed at 42 days (range, 7 to 720 days). Five-year survival was 92.9%, and 5-year freedom from major adverse cardiac and cerebral events was 75.2%. At 5 years, 2.7% of bypass grafts and 14.2% of percutaneous coronary intervention targets needed reintervention. CONCLUSIONS: Robotically assisted hybrid coronary intervention enables surgical treatment of multivessel coronary artery disease with minimal trauma. Perioperative results and intermediate-term outcomes meet the standards of open coronary artery bypass grafting. Recovery time is short, and reintervention rates are acceptable.