Acute impairment of regional myocardial glucose uptake in the apical ballooning (takotsubo) syndrome

BACKGROUND: Apical ballooning syndrome (ABS) is a poorly understood clinical entity characterized by acute, transient systolic dysfunction of the left ventricular (LV) apex in the absence of epicardial coronary artery disease and commonly associated with acute emotional stress. We report abnormal regional myocardial perfusion and glucose uptake in 4 consecutive ABS patients studied using positron emission tomography with 13N-ammonia and 18F-fluorodeoxyglucose within 72 hours of presentation with ABS. METHODS: All patients were postmenopausal females, 3 of whom had a major recent life stress event. Coronary angiography revealed no or minimal obstructive epicardial coronary artery disease. All patients exhibited reduced glucose uptake in the mid-LV and apical myocardial segments, which was out of proportion to perfusion abnormalities in half of the cases. CONCLUSION: In all 4 patients, affected regions subsequently recovered regional LV systolic function within 6 weeks.     

The Various Applications of 3D Printing in Cardiovascular Diseases

Purpose of Review

To highlight the various applications of 3D printing in cardiovascular disease and discuss its limitations and future direction.

Recent Findings

Use of handheld 3D printed models of cardiovascular structures has emerged as a facile modality in procedural and surgical planning as well as education and communication.

Summary

Three-dimensional (3D) printing is a novel imaging modality which involves creating patient-specific models of cardiovascular structures. As percutaneous and surgical therapies evolve, spatial recognition of complex cardiovascular anatomic relationships by cardiologists and cardiovascular surgeons is imperative. Handheld 3D printed models of cardiovascular structures provide a facile and intuitive road map for procedural and surgical planning, complementing conventional imaging modalities. Moreover, 3D printed models are efficacious educational and communication tools. This review highlights the various applications of 3D printing in cardiovascular diseases and discusses its limitations and future directions.

     

Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes

ObjectivesThe aim of this study was to assess 1-year clinical outcomes among high-risk patients with failed surgical mitral bioprostheses who underwent transseptal mitral valve-in-valve (MViV) with the SAPIEN 3 aortic transcatheter heart valve (THV) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial.BackgroundThe MITRAL trial is the first prospective study evaluating transseptal MViV with the SAPIEN 3 aortic THV in high-risk patients with failed surgical mitral bioprostheses.MethodsHigh-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis due to failed surgical mitral bioprostheses were prospectively enrolled. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year).ResultsThirty patients were enrolled between July 2016 and October 2017 (median age 77.5 years [interquartile range (IQR): 70.3 to 82.8 years], 63.3% women, median Society of Thoracic Surgeons score 9.4% [IQR: 5.8% to 12.0%], 80% in New York Heart Association functional class III or IV). The technical success rate was 100%. The primary performance endpoint in survivors was achieved in 96.6% (28 of 29) at 30 days and 82.8% (24 of 29) at 1 year. Thirty-day all-cause mortality was 3.3% and was unchanged at 1 year. The only death was due to airway obstruction after swallowing several pills simultaneously 29 days post-MViV. At 1-year follow-up, 89.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.6 mm Hg (interquartile range: 5.5 to 8.9 mm Hg), and all patients had MR grade ≤1+.ConclusionsTransseptal MViV in high-risk patients was associated with 100% technical success, low procedural complication rates, and very low mortality at 1 year. The vast majority of patients experienced significant symptom alleviation, and THV performance remained stable at 1 year.     

Next-Generation Sequencing of CYP2C19 in Stent Thrombosis: Implications for Clopidogrel Pharmacogenomics

Purpose

Describe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic variation detected by next-generation sequencing (NGS) with comprehensive annotation and functional studies.

Methods

Seventy ST cases on clopidogrel identified from the PLATO trial (n =?58) and Mayo Clinic biorepository (n =?12) were matched 1:1 with controls for age, race, sex, diabetes mellitus, presentation, and stent type. NGS was performed to cover the entire CYP2C19 gene. Assessment of exonic variants involved measuring in vitro protein expression levels. Intronic variants were evaluated for potential splicing motif variations.

Results

Poor metabolizers (n =?4) and rare CYP2C19*8, CYP2C19*15, and CYP2C19*11 alleles were identified only in ST cases. CYP2C19*17 heterozygote carriers were observed more frequently in cases (n =?29) than controls (n =?18). Functional studies of CYP2C19 exonic variants (n =?11) revealed 3 cases and only 1 control carrying a deleterious variant as determined by in vitro protein expression studies. Greater intronic variation unique to ST cases (n =?169) compared with controls (n =?84) was observed with predictions revealing 13 allele candidates that may lead to a potential disruption of splicing and a loss-of-function effect of CYP2C19 in ST cases.

Conclusion

NGS detected CYP2C19 poor metabolizers and paradoxically greater number of so-called rapid metabolizers in ST cases. Rare deleterious exonic variation occurs in 4%, and potentially disruptive intronic alleles occur in 16% of ST cases. Additional studies are required to evaluate the role of these variants in platelet aggregation and clopidogrel metabolism.

     

Long-term follow-up of patients undergoing closed transventricular mitral commissurotomy: a useful surrogate for percutaneous balloon mitral valvuloplasty?

OBJECTIVE: The aim of this study was to determine the long-term outcome and multivariate predictors of late events in patients who underwent transventricular mitral commissurotomy at the Mayo Clinic in the early 1960s. BACKGROUND. Percutaneous balloon mitral valvuloplasty is an important new procedure for which long-term follow-up data are not yet available. However, such data do exist for patients who have undergone transventricular mitral commissurotomy, a similar but older and more invasive procedure. METHODS. Follow-up data (mean duration 13.9 years) for 207 women and 60 men who underwent transventricular mitral commissurotomy were obtained from medical records, referring physicians, questionnaires and telephone interviews. Survival and survival free of repeat commissurotomy or mitral valve surgery were estimated with the Kaplan-Meier method. Cox proportional hazards model was used to determine predictors of survival and repeat mitral valve surgery. RESULTS. Postoperatively, 92% of patients had symptomatic improvement, which was sustained for at least 3 to 4 years in 78%. At 10, 15 and 20 years postoperatively, 79%, 67% and 55%, respectively, of patients were alive and 57%, 36% and 24%, respectively, were alive and free of repeat mitral valve surgery. At 10 years, 90% of all patients were free of transient or fixed cerebrovascular events. In multivariate analyses, atrial fibrillation, age and male gender were independently associated with death, whereas mitral valve calcification, cardiomegaly and mitral regurgitation independently predicted repeat mitral valve surgery. CONCLUSIONS. Long-term results after transventricular mitral commissurotomy are excellent in selected patients with symptomatic mitral stenosis. Because of similarities in patient selection and mechanisms of mitral valve dilation, similar favorable long-term outcomes may be expected after percutaneous balloon mitral valvuloplasty.     

Immediate and one-year outcome of intracoronary stent implantation in small coronary arteries with 2.5-mm stents

BACKGROUND: The role of coronary stenting in the treatment of stenoses in small coronary arteries with use of 2.5-mm stents is not well defined. METHODS AND RESULTS: Between January 1995 and August 1999, 651 patients with stenoses in small coronary arteries were treated with 2.5-mm stents (n = 108) or 2.5-mm conventional balloon angioplasty (BA) (n = 543). Patients who received treatment with both 2.5-mm and > or =3.0-mm stent placement or balloons were excluded. Procedural success and complication rates as well as 1-year follow-up outcomes were examined. Baseline clinical characteristics were similar between the two groups, except patients in the stent group were more likely to have hypertension and a family history of coronary artery disease and less likely to have prior myocardial infarction. Angiographic success rates were higher in the stent group (97.2% vs 90.2%, P =.02). In-hospital complication rates were comparable between the two groups. Among successfully treated patients, 1-year follow-up revealed no significant differences in the survival (96.2% vs 95.2%, P =.89) or the frequency of Q-wave myocardial infarction (0% vs 0.4%, P =.60) or coronary artery bypass grafting (8.4% vs 6.8%, P =.89) between the stent and BA groups, respectively. However, patients in the stent group were more likely to have adverse cardiac events (35.4% vs 22.1%, P =.05). Stent use after excluding GR II stent use, however, was not independently associated with reduced cardiac events at follow-up (relative risk 1. 3 [95% confidence interval 0.8-2.3], P =.30). CONCLUSIONS: Intracoronary stent implantation of stenoses in small coronary arteries with 2.5-mm stents can be carried out with high success and acceptable complication rates. However, compared with BA alone, stent use was not associated with improved outcome through 1 year of follow-up.     

Timing of coronary stent thrombosis in patients treated with ticlopidine and aspirin

In patients receiving coronary stents treated with aspirin and coumadin, the peak incidence of stent thrombosis occurs on the fifth and sixth days following the implantation procedure. Little is known about the timing of stent thrombosis in patients treated with aspirin and ticlopidine. We compared the timing of coronary stent thrombosis in patients treated with ticlopidine and aspirin with the timing in those receiving coumadin and aspirin. A retrospective databank analysis was performed and 39 patients were identified who experienced stent thrombosis after successful coronary stent implantation. Of these, 21 had been treated with ticlopidine and aspirin and 18 with coumadin and aspirin therapy. The median time from stent implantation to stent thrombosis in the ticlopidine and aspirin group was 12 hours (interquartile range 6 to 72 hours) compared with 4 days in the coumadin and aspirin group (interquartile range 21 to 68 hours) (p <0.0001). There was no significant difference between the timing of stent thrombosis in patients treated with abciximab in addition to ticlopidine and aspirin (median 17 hours, interquartile range 6 to 29) versus ticlopidine and aspirin patients who did not receive abciximab (median 11 hours, interquartile range 9 to 12, p = 0.57). Thus, in patients who receive coronary stents, stent thrombosis occurs much earlier after the procedure in patients treated with ticlopidine and aspirin than in patients treated with anticoagulation therapy.     

Correlates of procedural complications and a simple integer risk score for percutaneous coronary intervention

OBJECTIVES: Our goals were to identify clinical and angiographic risk factors associated with major cardiovascular complications of percutaneous coronary intervention (PCI) (in-hospital death, Q-wave myocardial infarction, urgent or emergent coronary artery bypass surgery and stroke) and to construct a simple score for risk stratification. BACKGROUND: Both clinical and angiographic features influence risk of PCIs. METHODS: Percutaneous coronary interventions performed between January 1, 1996, and December 31, 1999, were analyzed. Logistic regression and bootstrap methods were used to create an integer risk score for estimating the risk of procedural complications using baseline, angiographic and procedural characteristics. The risk score was tested in a validation-set consisting of all procedures performed in the year 2000. RESULTS: Among 5,463 procedures, 5 clinical and 3 angiographic variables were significantly correlated with procedural complications: cardiogenic shock, left main coronary artery disease, severe renal disease, urgent or emergent procedure, congestive heart failure class III or higher, thrombus, multivessel disease and older age. In the validation-set, the model fitted the data adequately; the average receiver operating characteristic curve area was 0.782 (standard deviation, 0.018). CONCLUSIONS: Eight variables were combined into a convenient bedside risk scoring system that estimates the risk of complications after PCIs.     

Emergency coronary artery bypass surgery for percutaneous coronary interventions: changes in the incidence, clinical characteristics, and indications from 1979 to 2003.

OBJECTIVES: The purpose of the current study was to evaluate the changes in incidence, clinical characteristics, and indications for emergency coronary artery bypass grafting (CABG) in patients undergoing percutaneous coronary intervention (PCI) from 1979 to 2003. BACKGROUND: Emergency CABG after PCI is associated with significant morbidity and mortality. METHODS: Data from 23,087 patients who underwent PCI at Mayo Clinic from 1979 to 2003 were analyzed. Patients were divided into three groups: the "pre-stent" era, 1979 to 1994 (n = 8,905); the "initial stent era," 1995 to 1999 (n = 7,605); and the "current stent era," 2000 to 2003 (n = 6,577). RESULTS: Although patients undergoing PCI in the recent time periods had more high-risk features, there was a significant decrease in the incidence of emergency CABG from 2.9% to 0.7% to 0.3% across the groups (p < 0.001). Patients requiring emergency surgery in the recent time periods had a higher prevalence of hypertension, prior revascularization, and left ventricular dysfunction (ejection fraction <40%), as well as more complex coronary lesions. Fewer patients in the current stent era had coronary artery dissections and abrupt vessel closure requiring emergency CABG. The in-hospital mortality rate for emergency CABG patients remains unchanged and ranges from 10% to 14%. CONCLUSIONS: The current study demonstrates that despite the increase in high-risk patients undergoing PCI, there has been a marked decrease in the incidence of patients requiring emergency CABG. However, the in-hospital mortality rate for those requiring emergency CABG remains high and unchanged.