Artificial intelligence approaches for phenotyping heart failure in U.S. Veterans Health Administration electronic health record.

AIMS: Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. METHODS AND RESULTS: The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). CONCLUSIONS: These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

Identification and outcomes of KDIGO-defined chronic kidney disease in 1.4 million U.S. Veterans with heart failure.

AIMS: According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes. METHODS AND RESULTS: Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m2, present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m2. Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations. CONCLUSION: Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria.

Characterization of Myocardial Injury With High-Sensitivity Troponin.

BACKGROUND: High-sensitivity troponin I, cardiac form (hs-cTnI) accelerates the assessment of acute coronary syndrome. Little has been documented about its performance, how it relates to different types of myocardial injury, and its impact on morbidity and mortality. This study sought to expand understanding of hs-cTnI by characterizing types of myocardial injury, the impact of comorbidities, and 30-day outcomes. METHODS: The study retrospectively evaluated 1,975 patients with hs-cTnI levels obtained in the emergency department or inpatient setting from June to September 2020. Troponin was considered elevated if it was higher than the 99th percentile for either sex. Charts were reviewed to determine the presence of myocardial injury. Troponin elevation was adjusted for demographics, comorbidities, and kidney dysfunction. Thirty-day mortality and readmission rates were calculated. RESULTS: Of 1,975 patients, 468 (24%) had elevated hs-cTnI, and 330 (17%) had at least 1 type of myocardial injury, type 2 myocardial infarction being the most frequent. Sensitivity and specificity using the 99th percentile as a cutoff were 99% and 92%, respectively. The average maximum hs-cTnI level was significantly higher for type 1 myocardial infarction (P < .001). Being male, Black, non-Hispanic, and a hospital inpatient were all associated with higher initial and peak hs-cTnI levels (P < .001). Elevated hs-cTnI level, age, heart disease, kidney dysfunction, and inpatient status were predictive of 30-day mortality on multivariate analysis. CONCLUSION: Elevated hs-cTnI levels in emergency department and inpatient settings occurs most commonly because of type 2 myocardial infarction. Maximum hs-cTnI level is associated with the patient's particular type of myocardial injury, certain demographics, and cardiovascular comorbidities, and it may be a predictor of 30-day outcomes.

Continuous EEG Characteristics in Critically ill Patients Presenting With Seizures Prior to Death From Cardiac Arrest.

Background: There have been limited reports about brain activity during cardiac arrest. Here we report 4 patients presenting with seizure who had cardiac arrest leading to their deaths while being on continuous video-EEG (cVEEG) monitoring and one-lead cardiac telemetry. Purpose: We illustrate characteristic stepwise EEG and EKG changes in these critically ill patients prior to their death. Research Design/Study Sample: All patients showed progressive broad spectrum of cardiac arrhythmias at or before the beginning of EEG suppression while there were no such changes seen in a control group of 4 randomly selected patients without cardiac arrest who had seizure on presentation and underwent cVEEG monitoring. Data Collection and Results: There was a progressive decline in EEG potentials associated with decreasing heart rate starting from the posterior region, more pronounced on the left, progressing to complete unilateral deactivation of the left fronto-central head regions while the right-sided networks became hyperactive before bilateral deactivation by the time of asystole. Conclusions: This case series provides a rare opportunity to compare EEG and EKG changes in patients who died while being on continuous EEG and EKG monitoring from hours to minutes prior to cardiac arrest and death.

Impact of the COVID-19 Pandemic on the Provision of Dialysis Service and Mortality in Veterans Receiving Maintenance Hemodialysis in the VA: An Interrupted Time-Series Analysis.

INTRODUCTION: According to the US Renal Data System (USRDS), patients with end-stage kidney disease (ESKD) on maintenance dialysis had higher mortality during early COVID-19 pandemic. Less is known about the effect of the pandemic on the delivery of outpatient maintenance hemodialysis and its impact on death. We examined the effect of pandemic-related disruption on the delivery of dialysis treatment and mortality in patients with ESKD receiving maintenance hemodialysis in the Veterans Health Administration (VHA) facilities, the largest integrated national healthcare system in the USA. METHODS: Using national VHA electronic health records data, we identified 7,302 Veterans with ESKD who received outpatient maintenance hemodialysis in VHA healthcare facilities during the COVID-19 pandemic (February 1, 2020, to December 31, 2021). We estimated the average change in the number of hemodialysis treatments received and deaths per 1,000 patients per month during the pandemic by conducting interrupted time-series analyses. We used seasonal autoregressive moving average (SARMA) models, in which February 2020 was used as the conditional intercept and months thereafter as conditional slope. The models were adjusted for seasonal variations and trends in rates during the pre-pandemic period (January 1, 2007, to January 31, 2020). RESULTS: The number (95% CI) of hemodialysis treatments received per 1,000 patients per month during the pre-pandemic and pandemic periods were 12,670 (12,525-12,796) and 12,865 (12,729-13,002), respectively. Respective all-cause mortality rates (95% CI) were 17.1 (16.7-17.5) and 19.6 (18.5-20.7) per 1,000 patients per month. Findings from SARMA models demonstrate that there was no reduction in the dialysis treatments delivered during the pandemic (rate ratio: 0.999; 95% CI: 0.998-1.001), but there was a 2.3% (95% CI: 1.5-3.1%) increase in mortality. During the pandemic, the non-COVID hospitalization rate was 146 (95% CI: 143-149) per 1,000 patients per month, which was lower than the pre-pandemic rate of 175 (95% CI: 173-176). In contrast, there was evidence of higher use of telephone encounters during the pandemic (3,023; 95% CI: 2,957-3,089), compared with the pre-pandemic rate (1,282; 95% CI: 1,241-1,324). CONCLUSIONS: We found no evidence that there was a disruption in the delivery of outpatient maintenance hemodialysis treatment in VHA facilities during the COVID-19 pandemic and that the modest rise in deaths during the pandemic is unlikely to be due to missed dialysis.

Renin-Angiotensin Inhibition and Outcomes in HFrEF and Advanced Kidney Disease.

BACKGROUND: Renin-angiotensin system inhibitors improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, less is known about their effectiveness in patients with HFrEF and advanced kidney disease. METHODS: In the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), 1582 patients with HFrEF (ejection fraction ≤40%) had advanced kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2). Of these, 829 were not receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prior to admission, of whom 214 were initiated on these drugs prior to discharge. We calculated propensity scores for receipt of these drugs for each of the 829 patients and assembled a matched cohort of 388 patients, balanced on 47 baseline characteristics (mean age 78 years; 52% women; 10% African American; 73% receiving beta-blockers). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated comparing 2-year outcomes in 194 patients initiated on ACE inhibitors or ARBs to 194 patients not initiated on those drugs. RESULTS: The combined endpoint of heart failure readmission or all-cause mortality occurred in 79% and 84% of patients initiated and not initiated on ACE inhibitors or ARBs, respectively (HR associated with initiation, 0.79; 95% CI, 0.63-0.98). Respective HRs (95% CI) for the individual endpoints of - Respective HRs (95% CI) for the individual endpoints of all-cause mortality and heart failure readmission were 0.81 (0.63-1.03) and 0.63 (0.47-0.85). CONCLUSIONS: The findings from our study add new information to the body of cumulative evidence that suggest that renin-angiotensin system inhibitors may improve clinical outcomes in patients with HFrEF and advanced kidney disease. These hypothesis-generating findings need to be replicated in contemporary patients.

Imaging modality for left ventricular ejection fraction estimation and effect of implantable cardioverter-defibrillator on mortality in patients with heart failure.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) improve outcomes in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35%. Less is known about whether outcomes varied between the 2 noninvasive imaging modalities used to estimate LVEF-2-dimensional echocardiography (2DE) and multigated acquisition radionuclide ventriculography (MUGA)-which use different principles (geometric vs count-based, respectively). OBJECTIVE: The purpose of this study was to examine whether the effect of ICD on mortality in patients with HF and LVEF ≤35% varied on the basis of LVEF measured by 2DE or MUGA. METHODS: Of the 2521 patients with HF with LVEF ≤35% in the Sudden Cardiac Death in Heart Failure Trial, 1676 (66%) were randomized to either placebo or ICD, of whom 1386 (83%) had LVEF measured by 2DE (n = 971) or MUGA (n = 415). Hazard ratios (HRs) and 97.5% confidence intervals (CIs) for mortality associated with ICD were estimated overall, checking for interaction, and within the 2 imaging subgroups. RESULTS: Of the 1386 patients in the present analysis, all-cause mortality occurred in 23.1% (160 of 692) and 29.7% (206 of 694) of patients randomized to ICD or placebo, respectively (HR 0.77; 97.5% CI 0.61-0.97), which is consistent with that in 1676 patients in the original report. HRs (97.5% CIs) for all-cause mortality in the 2DE and MUGA subgroups were 0.79 (0.60-1.04) and 0.72 (0.46-1.11), respectively (P = .693 for interaction). Similar associations were observed for cardiac and arrhythmic mortalities. CONCLUSION: We found no evidence that in patients with HF and LVEF ≤35%, the effect of ICD on mortality varied by the noninvasive imaging method used to measure LVEF.

Risk of Stroke in Older Adults With Heart Failure.

Heart failure (HF) is a risk factor for incident stroke. However, less is known about the independent nature of this association and to what extent various baseline characteristics may mediate this risk. Of the 5,795 community-dwelling adults aged ≥65 years in the Cardiovascular Health Study, 5,448 were free of baseline stroke, of whom 229 had baseline HF. We used a multivariable-adjusted Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for centrally adjudicated incident stroke associated with HF. Participants had a mean age of 73 years, 58% were women, and 15% were African-American. During 23 years of follow-up, incident stroke occurred in 18.8% and 19.3% of those with and without HF, respectively, but the time to first stroke was shorter in those with HF (age-gender-race-adjusted HR 1.64, 95% CI 1.21 to 2.25). The association remained essentially unchanged after adjustments for tobacco, alcohol, and physical activity (HR 1.63, 95% CI 1.21 to 2.24), attenuated after adjustment for hypertension, atrial fibrillation, myocardial infarction, and diabetes mellitus (HR 1.26, 95% CI 0.92 to 1.72), and further attenuated after additional adjustment for 10 baseline functional and subclinical variables (HR 1.05, 95% CI 0.76 to 1.46). In conclusion, despite a similar 23-year stroke incidence, time to first stroke was shorter in older adults with HF than without. However, this extra risk appears to be mediated primarily by 4 cardiovascular diseases that are also risk factors for HF. These findings highlight the importance of the primary prevention of these HF risk factors to reduce the extra risk of stroke in HF.

Initiation of anti-hypertensive drugs and outcomes in patients with heart failure with preserved ejection fraction and persistent hypertension.

BACKGROUND: National heart failure (HF) guidelines recommend that in patients with HF with preserved ejection fraction (EF;HFpEF) and hypertension, systolic blood pressure (SBP) should be maintained below 130 mmHg. The objective of the study is to examine the association between initiation of anti-hypertensive drugs and outcomes in patients with HFpEF with persistent hypertension. METHODS: Of the 8873 hospitalized patients with HFpEF (EF ≥50%) with a history of hypertension without renal failure in Medicare-linked OPTIMIZE-HF, 3315 had a discharge SBP ≥130 mmHg, of whom 1971 were not receiving anti-hypertensive drugs, thiazides and calcium channel blockers, before hospitalization. Of these, 366 received discharge prescriptions for those drugs. We assembled a propensity score-matched cohort of 365 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 37 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with anti-hypertensive drug initiation were estimated in the matched cohort. RESULTS: Matched patients (n = 730) had a mean age of 78 years; 67% were women and 17% African Americans. During 6 (median 2.5) years of follow-up, 66% of the patients died and 45% had HF readmission. HRs (95% CIs) for all-cause mortality at 30 days, 12 months and 6 years associated with anti-hypertensive drug initiation were 0.64 (0.30-1.36), 0.70 (0.51-0.97), and 0.95 (0.79-1.13), respectively. Respective HRs (95% CIs) for HF readmission were 1.65 (0.97-2.80), 1.18 (0.90-1.56) and 1.09 (0.88-1.35). CONCLUSIONS: Among hospitalized older patients with HFpEF with uncontrolled hypertension, the initiation of therapy with anti-hypertensive drugs was not associated with all-cause mortality or hospital readmission.

Initiation of Anti-Hypertensive Drugs and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: In patients with heart failure with reduced ejection fraction (HFrEF) and hypertension, systolic blood pressure is recommended to be maintained below 130 mmHg, although this has not been shown to be associated with improved outcomes. We examined the association between anti-hypertensive drug initiation and outcomes in patients with HFrEF. METHODS: In the Medicare-linked OPTIMIZE-HF, 7966 patients with HFrEF (ejection fraction ≤40%) without renal failure were not receiving anti-hypertensive drugs before hospitalization, of whom 692 received discharge prescriptions for those drugs (thiazides and calcium channel blockers). We assembled a propensity score-matched cohort of 687 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 38 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CIs) for outcomes associated with anti-hypertensive drug initiation were estimated in the matched cohort. RESULTS: Matched patients (n = 1374) had a mean age of 74 years, 41% were female, 17% were African-American, 66% were discharged on renin-angiotensin system inhibitors and beta blockers, and 10% on aldosterone antagonists. During 6 (median 2.5) years of follow-up, 70% of the patients died and 53% had heart failure readmission. Anti-hypertensive drug initiation was not significantly associated with all-cause mortality (HR, 0.95; 95% CI, 0.83-1.07) or heart failure readmission (HR, 0.93; 95% CI, 0.80-1.07). Similar associations were observed during 30 days and 12 months of follow-up. CONCLUSIONS: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, initiation of an anti-hypertensive drug was not associated with a lower risk of all-cause mortality or hospital readmission.

Is statin therapy safe and effective in patients with chronic Kidney disease?

Chronic kidney disease (CKD) is associated with dyslipidemia and increased cardiovascular risk. This elevated risk for cardiovascular events exists even in the largest subpopulation with milder stages of CKD, prior to the development of significant reductions in renal excretory function. Statin therapy is a critical component of primary and secondary cardiovascular prevention efforts for at-risk patients. Efficacy in the CKD population, however, has appeared less robust across the spectrum of CKD, particularly in hemodialysis patients. This article will review the current state of knowledge on statin therapy in CKD, effects on renal outcomes, safety in this population and alternative lipid therapies.

Renal Denervation Therapy for Drug-Resistant Hypertension: Does It Still Work?

OPINION STATEMENT: Hypertension is a global public health problem affecting one-fourth of the world's population. A subset of these patients with resistant hypertension presents a particular management problem and suffers a marked increase in cardiovascular risk. Treatment options have been limited, but the past decade has witnessed the emergence of catheter-based renal denervation to interrupt the sympathetic nervous system, long considered to play an important role in the development and maintenance of hypertension. Phase 1 and 2 studies reported remarkable reductions in blood pressure and sparked an excessive exuberance that ground to a halt with negative results of the SYMPLICITY HTN-3 pivotal trial. The subsequent and sober reappraisal has shed light on potential failure modes. Armed with appropriately cautious optimism, the field has resumed its move forward to realize the potential for therapeutic application in hypertension and other conditions characterized by sympathetic overactivity. This article summarizes the rich experimental data, early surgical experience, and available clinical trial results for catheter platforms. It concludes with discussion of knowledge gaps, lessons learned, and future directions.

Evolution and Controllability of Cancer Networks: A Boolean Perspective.

Cancer forms a robust system capable of maintaining stable functioning (cell sustenance and proliferation) despite perturbations. Cancer progresses as stages over time typically with increasing aggressiveness and worsening prognosis. Characterizing these stages and identifying the genes driving transitions between them is critical to understand cancer progression and to develop effective anti-cancer therapies. In this work, we propose a novel model for the `cancer system' as a Boolean state space in which a Boolean network, built from protein-interaction and gene-expression data from different stages of cancer, transits between Boolean satisfiability states by "editing" interactions and "flipping" genes. Edits reflect rewiring of the PPI network while flipping of genes reflect activation or silencing of genes between stages. We formulate a minimization problem min flip to identify these genes driving the transitions. The application of our model (called BoolSpace) on three case studies-pancreatic and breast tumours in human and post spinal-cord injury (SCI) in rats-reveals valuable insights into the phenomenon of cancer progression: (i) interactions involved in core cell-cycle and DNA-damage repair pathways are significantly rewired in tumours, indicating significant impact to key genome-stabilizing mechanisms; (ii) several of the genes flipped are serine/threonine kinases which act as biological switches, reflecting cellular switching mechanisms between stages; and (iii) different sets of genes are flipped during the initial and final stages indicating a pattern to tumour progression. Based on these results, we hypothesize that robustness of cancer partly stems from "passing of the baton" between genes at different stages-genes from different biological processes and/or cellular components are involved in different stages of tumour progression thereby allowing tumour cells to evade targeted therapy, and therefore an effective therapy should target a "cover set" of these genes. A C/C++ implementation of BoolSpace is freely available at: http://www.bioinformatics.org.au/tools-data.

Limitations of closing percutaneous transthoracic ventricular access ports using a commercial collagen vascular closure device.

INTRODUCTION: Closed-chest access and closure of direct cardiac punctures may enable a range of therapeutic procedures. We evaluate the safety and feasibility of closing percutaneous direct ventricular access sites using a commercial collagen-based femoral artery closure device. METHODS: Yorkshire swine underwent percutaneous transthoracic left ventricular access (n = 13). The access port was closed using a commercial collagen-based vascular closure device (Angio-Seal, St. Jude Medical) with or without prior separation of the pericardial layers by instillation of fluid into the pericardial space ("permissive pericardial tamponade"). After initial nonsurvival feasibility experiments (n = 6); animals underwent 1-week (n = 3) or 6-week follow-up (n = 4). RESULTS: In naïve animals, the collagen plug tended to deploy outside the parietal pericardium, where it failed to accomplish hemostasis. "Permissive pericardial tamponade" was created under MRI, and accomplished early hemostasis by allowing the collagen sponge to seat on the epicardial surface inside the pericardium. After successful closure, six of seven animals accumulated a large pericardial effusion 5 ± 1 days after closure. Despite percutaneous drainage during 6-week follow-up, the large pericardial effusion recurred in half, and was lethal in one. CONCLUSIONS: A commercial collagen-based vascular closure device may achieve temporary but not durable hemostasis when closing a direct left ventricular puncture port, but only after intentional pericardial separation. These insights may contribute to development of a superior device solution. Elective clinical application of this device to close apical access ports should be avoided.

Mitral cerclage annuloplasty, a novel transcatheter treatment for secondary mitral valve regurgitation: initial results in swine.

OBJECTIVES: We developed and tested a novel transcatheter circumferential annuloplasty technique to reduce mitral regurgitation in porcine ischemic cardiomyopathy. BACKGROUND: Catheter-based annuloplasty for secondary mitral regurgitation exploits the proximity of the coronary sinus to the mitral annulus, but is limited by anatomic variants and coronary artery entrapment. METHODS: The procedure, "cerclage annuloplasty," is guided by magnetic resonance imaging (MRI) roadmaps fused with live X-ray. A coronary sinus guidewire traverses a short segment of the basal septal myocardium to re-enter the right heart where it is exchanged for a suture. Tension is applied interactively during imaging and secured with a locking device. RESULTS: We found 2 feasible suture pathways from the great cardiac vein across the interventricular septum to create cerclage. Right ventricular septal re-entry required shorter fluoroscopy times than right atrial re-entry, which entailed a longer intramyocardial traversal but did not cross the tricuspid valve. Graded tension progressively reduced septal-lateral annular diameter, but not end-systolic elastance or regional myocardial function. A simple arch-like device protected entrapped coronary arteries from compression even during supratherapeutic tension. Cerclage reduced mitral regurgitation fraction (from 22.8 +/- 12.7% to 7.2 +/- 4.4%, p = 0.04) by slice tracking velocity-encoded MRI. Flexible cerclage reduced annular size but preserved annular motion. Cerclage also displaced the posterior annulus toward the papillary muscles. Cerclage introduced reciprocal constraint to the left ventricular outflow tract and mitral annulus that enhanced leaflet coaptation. A sample of human coronary venograms and computed tomography angiograms suggested that most have suitable venous anatomy for cerclage. CONCLUSIONS: Transcatheter mitral cerclage annuloplasty acutely reduces mitral regurgitation in porcine ischemic cardiomyopathy. Entrapped coronary arteries can be protected. MRI provided insight into the mechanism of cerclage action.

Antegrade percutaneous closure of membranous ventricular septal defect using X-ray fused with magnetic resonance imaging.

OBJECTIVES: We hypothesized that X-ray fused with magnetic resonance imaging (XFM) roadmaps might permit direct antegrade crossing and delivery of a ventricular septal defect (VSD) closure device and thereby reduce procedure time and radiation exposure. BACKGROUND: Percutaneous device closure of membranous VSD is cumbersome and time-consuming. The procedure requires crossing the defect retrograde, snaring and exteriorizing a guidewire to form an arteriovenous loop, then delivering antegrade a sheath and closure device. METHODS: Magnetic resonance imaging roadmaps of cardiac structures were obtained from miniature swine with spontaneous VSD and registered with live X-ray using external fiducial markers. We compared antegrade XFM-guided VSD crossing with conventional retrograde X-ray-guided crossing for repair. RESULTS: Antegrade XFM crossing was successful in all animals. Compared with retrograde X-ray, antegrade XFM was associated with shorter time to crossing (167 +/- 103 s vs. 284 +/- 61 s; p = 0.025), shorter time to sheath delivery (71 +/- 32 s vs. 366 +/- 145 s; p = 0.001), shorter fluoroscopy time (158 +/- 95 s vs. 390 +/- 137 s; p = 0.003), and reduced radiation dose-area product (2,394 +/- 1,522 mG.m(2) vs. 4,865 +/- 1,759 mG.m(2); p = 0.016). CONCLUSIONS: XFM facilitates antegrade access to membranous VSD from the right ventricle in swine. The simplified procedure is faster and reduces radiation exposure compared with the conventional retrograde approach.

Very late thrombosis of drug-eluting stents: a brief literature review and case example.

Thrombosis late after implantation is an infrequent but increasingly recognized complication following revascularization with drug-eluting stents (DES). The window of vulnerability for this complication with DES remains undefined. Intermediate-term follow up from pivotal trials and registries suggests continuous separation of event curves out to at least 3 years. We briefly review the evolving body of literature on DES thrombosis and report a case of very late thrombosis 53 months after implantation of a sirolimus-eluting stent. The event occurred despite chronic aspirin monotherapy and represents the longest latency from implantation to thrombosis described in the literature for a DES.

Real-time MR imaging-guided laser atrial septal puncture in swine.

PURPOSE: The authors performed this study to report their initial preclinical experience with real-time magnetic resonance (MR) imaging-guided atrial septal puncture by using a MR imaging-conspicuous blunt laser catheter that perforates only when energized. MATERIALS AND METHODS: The authors customized a 0.9-mm clinical excimer laser catheter with a receiver coil to impart MR imaging visibility at 1.5 T. Seven swine underwent laser transseptal puncture under real-time MR imaging. MR imaging signal-to-noise ratio profiles of the device were obtained in vitro. Tissue traversal force was tested with a calibrated meter. Position was corroborated with pressure measurements, oximetry, angiography, and necropsy. Intentional non-target perforation simulated serious complication. RESULTS: Embedded MR imaging antennae accurately reflected the position of the laser catheter tip and profile in vitro and in vivo. Despite having an increased profile from the microcoil, the 0.9-mm laser catheter traversed in vitro targets with similar force (0.22 N +/- 0.03) compared with the unmodified laser. Laser puncture of the atrial septum was successful and accurate in all animals. The laser was activated an average of 3.8 seconds +/- 0.4 before traversal. There were no sequelae after 6 hours of observation. Necropsy revealed 0.9-mm holes in the fossa ovalis in all animals. Intentional perforation of the aorta and atrial free wall was evident immediately. CONCLUSIONS: MR imaging-guided laser puncture of the interatrial septum is feasible in swine and offers controlled delivery of perforation energy by using an otherwise blunt catheter. Instantaneous soft tissue imaging provides immediate feedback on safety.

Technology preview: X-ray fused with magnetic resonance during invasive cardiovascular procedures.

BACKGROUND: We have developed and validated a system for real-time X-ray fused with magnetic resonance imaging, MRI (XFM), to guide catheter procedures with high spatial precision. Our implementation overlays roadmaps-MRI-derived soft-tissue features of interest-onto conventional X-ray fluoroscopy. We report our initial clinical experience applying XFM, using external fiducial markers, electrocardiogram (ECG)- gating, and automated real-time correction for gantry and table movement. METHODS: This prospective case series for technical development was approved by the NHLBI Institutional Review Board and included 19 subjects. Multimodality external fiducial markers were affixed to patients' skin before MRI, which included contrast-enhanced, 3D T1-weighted, or breath-held and ECG-gated 2D steady state free precession imaging at 1.5T. MRI-derived roadmaps were manually segmented while patients were transferred to a calibrated X-ray fluoroscopy system. Image spaces were registered using the fiducial markers and thereafter permitted unrestricted gantry rotation, table panning, and magnification changes. Static and ECG-gated MRI data were transformed from 3D to 2D to correspond with gantry and table position and combined with live X-ray images. RESULTS: Clinical procedures included graft coronary arteriography, right ventricular free-wall biopsy, and iliac and femoral artery recanalization and stenting. MRI roadmaps improved operator confidence, and in the biopsy cases, outperformed the best available alternative imaging modality. Registration errors were increased when external fiducial markers were affixed to more mobile skin positions, such as over the abdomen. CONCLUSION: XFM using external fiducial markers is feasible during X-ray guided catheter treatments. Multimodality image fusion may prove a useful adjunct to invasive cardiovascular procedures.

Interventional cardiovascular procedures guided by real-time MR imaging: an interactive interface using multiple slices, adaptive projection modes and live 3D renderings.

PURPOSE: To develop and test a novel interactive real-time MRI environment that facilitates image-guided cardiovascular interventions. MATERIALS AND METHODS: Color highlighting of device-mounted receiver coils, accelerated imaging of multiple slices, adaptive projection modes, live three-dimensional (3D) renderings and other interactive features were utilized to enhance navigation of devices and targeting of tissue. RESULTS: Images are shown from several catheter-based interventional procedures performed in swine that benefit from this custom interventional MRI interface. These include endograft repair of aortic aneurysm, balloon septostomy of the cardiac interatrial septum, angioplasty and stenting, and endomyocardial cell injection, all using active catheters containing MRI receiver coils. CONCLUSION: Interactive features not available on standard clinical scanners enhance real-time MRI for guiding cardiovascular interventional procedures.