Intracoronary Imaging and Physiology to Guide PCI: Are We Ready for a Class I Guideline Recommendation?

PURPOSE OF REVIEW: Over the last decade, there has been a plethora of evidence to support the utilization of intravascular coronary imaging and physiological assessment to guide percutaneous coronary interventions (PCI). While there is a class I recommendation for the use of coronary physiology to guide PCI, the use of intravascular coronary imaging remains a class IIa recommendation. Herein, we aimed to review the recent scientific evidence from major trials highlighting the consideration for a future class I guideline recommendation for the use of intracoronary imaging. RECENT FINDINGS: The benefits of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) to guide and optimize PCI have been demonstrated in several large trials. These trials have demonstrated that IVUS reduces major adverse cardiovascular events. Similarly, intracoronary physiology has been demonstrated to be an important tool to guide revascularization decision-making and been associated with a lower incidence of death, non-fatal myocardial infarction, and repeat revascularization compared with angiography alone. With existing clinical outcomes data on the benefit of intracoronary physiology and imaging-guided PCI as well as forthcoming data from ongoing trials regarding the use of these modalities, the interventional cardiology community is bound to transition from routine PCI to precision-, image-, and physiology-guided PCI.

Midterm Durability and Structural Valve Degeneration of Transcatheter Aortic Valve Replacement in a Federal Facility.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR), previously reserved for patients of intermediate to prohibitive surgical risk, has now been expanded to patients of any surgical risk with severe aortic stenosis. Bioprostheses are prone to structural valve degeneration (SVD), a progressive and multifactorial process that limits valve durability. As the population undergoing TAVR shifts toward a lower-risk and younger profile, long-term durability is a crucial determinant for patient outcomes. Our objective was to determine the incidence and risk factors of SVD at midterm follow-up in a veteran TAVR population. METHODS: Patients undergoing TAVR at our federal facility were retrospectively evaluated for SVD and other endpoints with standardized consensus criteria. Multivariable Cox proportional hazards analysis was performed to evaluate risk factors for mortality and SVD. RESULTS: From 2013 to 2020, 344 patients (median age, 78 years) underwent TAVR. Survival from all-cause mortality was 91.3% at 1 year, 75.1% at 3 years, and 61.7% at 5 years. Cumulative freedom from SVD was 98.2% at 1 year, 96.5% at 3 years, and 93.7% at 5 years. All 13 patients with SVD met hemodynamic criteria, and 1 required intervention. Median time to hemodynamic SVD was 1.04 years. Independent risk factors for SVD included age (hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.86 to 0.99) and valve size (HR = 0.19, 95% CI: 0.04 to 0.89). CONCLUSIONS: SVD was evident at a low but detectable rate at 5-year follow-up. Further understanding of TAVR biomechanics as well as continued longer-term follow-up will be essential for informing patient-specific risk of SVD.

Development of the Minimalist Approach for Transcatheter Aortic Valve Replacement at a Veterans Affairs Medical Center.

OBJECTIVES: While a minimalist transcatheter aortic valve replacement (TAVR) approach has shown safety and efficacy at civilian hospitals, limited data exist regarding developing this approach at Veterans Affairs (VA) medical centers (VAMCs). We implemented TAVR with minimalist approach (MA) using conscious sedation (CS) with transthoracic echocardiography (TTE) and compared safety and outcomes with general anesthesia (GA) with transesophageal echocardiography (TEE) at a university-affiliated VAMC. METHODS: A total of 258 patients underwent transfemoral TAVR at a VAMC between November 2013 and October 2019. Ninety-three patients underwent GA/TEE and 165 patients underwent CS/TTE with dexmedetomidine and remifentanil. Propensity-score matching with nearest-neighbor matching was used to account for baseline differences, yielding 227 participants (81 GA, 146 CS). RESULTS: MA-TAVR had no effect on 30-day mortality or paravalvular leakage. No differences were found in permanent pacemaker implantation, major vascular complications, or postoperative hemodynamics. In this population, MA-TAVR did not reduce procedural time, hospital length of stay, or intensive care unit length of stay. CONCLUSIONS: Unlike civilian hospitals, MA with CS/TTE did not reduce overall length of stay in the veteran population; however, it was safe and effective for transfemoral TAVR without impacting clinical outcomes of mortality, major vascular complications, and paravalvular leakage.

A Randomized Controlled Trial of Prasugrel for Prevention of Early Saphenous Vein Graft Thrombosis.

OBJECTIVES: To test whether administration of prasugrel after coronary artery bypass grafting (CABG) reduces saphenous vein graft (SVG) thrombosis. Use of aspirin after CABG improves graft patency, but administration of other antiplatelet agents has yielded equivocal results. METHODS: We performed a double-blind trial randomizing patients to prasugrel or placebo after CABG at four United States centers. Almost all patients were receiving aspirin. Follow-up angiography, optical coherence tomography (OCT), intravascular ultrasound (IVUS), and near-infrared spectroscopy (NIRS) were performed at 12 months. The primary efficacy endpoint was prevalence of OCT-detected SVG thrombus. The primary safety endpoint was incidence of Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) severe bleeding. RESULTS: The study was stopped early due to slow enrollment after randomizing 84 patients. Mean age was 64 ± 6 years; 98% of the patients were men. Follow-up angiography was performed in 59 patients. IVUS was performed in 52 patients, OCT in 53 patients, and NIRS in 33 patients. Thrombus was identified by OCT in 56% vs 50% of patients in the prasugrel vs placebo groups, respectively (P=.78). Angiographic SVG failure occurred in 24% of patients in the prasugrel arm vs 40% in the placebo arm (P=.19). The 1-year incidence of major adverse cardiovascular events was 14.3% vs 2.4% in the prasugrel and placebo groups, respectively (P=.20), without significant differences in GUSTO severe bleeding (P=.32). CONCLUSION: Early SVG failure occurred in approximately one-third of patients. Prasugrel did not decrease prevalence of SVG thrombus 12 months after CABG.

Outcomes of Veterans Undergoing TAVR Within Veterans Affairs Medical Centers: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

OBJECTIVES: This study sought to describe clinical and procedural characteristics of veterans undergoing transcatheter aortic valve replacement (TAVR) within U.S. Department of Veterans Affairs (VA) centers and to examine their association with short- and long-term mortality, length of stay (LOS), and rehospitalization within 30 days. BACKGROUND: Veterans with severe aortic stenosis frequently undergo TAVR at VA medical centers. METHODS: Consecutive veterans undergoing TAVR between 2012 and 2017 were included. Patient and procedural characteristics were obtained from the VA Clinical Assessment, Reporting, and Tracking system. The primary outcomes were 30-day and 1-year survival, LOS >6 days, and rehospitalization within 30 days. Logistic regression and Cox proportional hazards analyses were performed to evaluate the associations between pre-procedural characteristics and LOS and rehospitalization. RESULTS: Nine hundred fifty-nine veterans underwent TAVR at 8 VA centers during the study period, 860 (90%) by transfemoral access, 50 (5%) transapical, 36 (3.8%) transaxillary, and 3 (0.3%) transaortic. Men predominated (939 of 959 [98%]), with an average age of 78.1 years. There were 28 deaths within 30 days (2.9%) and 134 at 1 year (14.0%). Median LOS was 5 days, and 141 veterans were rehospitalized within 30 days (14.7%). Nonfemoral access (odds ratio: 1.74; 95% confidence interval [CI]: 1.10 to 2.74), heart failure (odds ratio: 2.51; 95% CI: 1.83 to 3.44), and atrial fibrillation (odds ratio: 1.40; 95% CI: 1.01 to 1.95) were associated with increased LOS. Atrial fibrillation was associated with 30-day rehospitalization (hazard ratio: 1.79; 95% CI: 1.22 to 2.63). CONCLUSIONS: Veterans undergoing TAVR at VA centers are predominantly elderly men with significant comorbidities. Clinical outcomes of mortality and rehospitalization at 30 days and 1-year mortality compare favorably with benchmark outcome data outside the VA.

Dual antiplatelet therapy in non-ST elevation acute coronary syndromes at Veterans Affairs Hospitals.

OBJECTIVE: Current guidelines recommend that patients with non-ST elevation acute coronary syndromes (NSTEACS) receive dual antiplatelet therapy (DAPT) early in hospitalisations. However, observational studies suggest that this rarely occurs. We evaluated site-specific variation and clinical outcomes associated with early DAPT among patients undergoing angiography for NSTEACS. METHODS: In this observational analysis, we identified patients undergoing angiography for NSTEACS in Veterans Affairs hospitals from 2008 to 2016 and assessed characteristics and site variation associated with early DAPT (administration <24 hours of admission). Using propensity matching, we compared time to revascularisation, recurrent myocardial infarction (MI) and mortality between those receiving early DAPT and those not receiving early DAPT (administration ≥24 hours). RESULTS: Of 45 569 patients undergoing angiography for NSTEACS, 15 084 (33%) received early DAPT. Early DAPT was more frequent in patients with non-ST elevation MI, prior surgical revascularisation and among patients undergoing revascularisation. There was a greater than twofold difference in early DAPT across sites, independent of patient characteristics (median OR 2.43, 95% CI 2.28 to 2.55). There was no difference in time topercutaneous coronary intervention (PCI) between groups, but a significant delay to surgical revascularisation with early DAPT (median 4 vs 3 days, p<0.001) without reduction in hazard of death or MI (HR 1.08, 95% CI 1.00 to 1.16) and similar results demonstrated in the subgroup of patients undergoing revascularisation (HR 1.02, 95% CI 0.91 to 1.13). CONCLUSION: Among NSTEACS patients undergoing coronary angiography, early DAPT was not associated with improvement of outcomes but was associated with delays in surgical revascularisation.

Veterans Affairs Heart Team Experience With Transcatheter Aortic Valve Replacement and Minimally Invasive Surgical Aortic Valve Replacement.

OBJECTIVES: Aortic valve disease is prevalent in the veteran population. Transcatheter aortic valve replacement (TAVR) and minimally invasive surgical aortic valve replacement (MIAVR) are minimally invasive approaches predominantly performed at higher-volume cardiac centers. The study aim was to evaluate our experience with minimally invasive techniques at a Veterans Affairs Medical Center (VAMC), since outcomes from lower-volume federal facilities are relatively unknown. METHODS: This study examined retrospective data from 228 consecutive patients who underwent treatment for isolated aortic valve disease with MIAVR or TAVR via intent-to-treat at a VAMC between January 2011 and July 2017. Perioperative outcomes were analyzed using Stata version 15. RESULTS: Operative mortality was 1.1% for MIAVR and 0.7% for TAVR (Χ² P=.79). Median length of hospital stay was 10 days (interquartile range [IQR], 7-14 days) for MIAVR and 4 days for TAVR (IQR, 3-6 days; Mann-Whitney P<.001). Postoperative new-onset atrial fibrillation occurred in 52% of MIAVR patients and 5.2% of TAVR patients (Χ² P<.001). Stroke occurred in 2.2% of MIAVR patients and 3.0% of TAVR patients (Χ² P=.71). In patients who underwent MIAVR, 5.4% required placement of a permanent pacemaker postoperatively, compared with 14% of TAVR patients (Χ² P=.04). Mild paravalvular leak (PVL) affected 2.2% of MIAVR and 28% of TAVR patients, with moderate PVL reported in 2.2% of MIAVR and 3% of TAVR patients (Χ² P<.001). CONCLUSIONS: The VAMC heart team offers MIAVR and TAVR to veterans with isolated aortic valve disease, and has achieved excellent outcomes despite relatively lower case volumes. Both offer excellent hemodynamic results, with low mortality in a complex population.

Evolution of Veterans Affairs Transcatheter Aortic Valve Replacement Program: The First 100 Patients.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a widely established alternative to surgery in intermediate- and high-risk patients. TAVR program development within the Veterans Affairs (VA) system has been previously described. However, national TAVR registries do not capture VA outcomes data, and few data have been reported regarding TAVR outcomes at lower-volume federal institutions. The study aim was to demonstrate the evolution of a successful VA TAVR program. METHODS: A retrospective analysis was performed of the first 100 TAVR patients at San Francisco VA Medical Center. Mortality and major complications were evaluated. RESULTS: Between 25th November 2013 and 31st August 2016, a total of 100 TAVR procedures was performed at the authors' institution. The mean patient age was 79.7 ± 8.7 years. Patients underwent TAVR via percutaneous-transfemoral (n = 90), surgical cutdown-transfemoral (n = 8), or transapical (n = 2) approaches. The valve systems employed were Edwards SAPIEN (n = 16), SAPIEN XT (n = 31), SAPIEN 3 (n = 23), and Medtronic CoreValve (n = 16) and CoreValve Evolut R (n = 14). The overall device success was 96%. TAVR-in-TAVR was required in the remaining 4% of patients, and was successful. All-cause procedural mortality was 1%. Complications included tamponade (1%), stroke (2%), temporary hemodialysis (1%), vascular injuries requiring intervention (4%), and permanent pacemaker implantation (14%). There were no conversions to surgical aortic valve replacement. Twenty-two (22%) patients had mild, two (2%) had moderate, and none (0%) had severe paravalvular leakage. The post-procedure aortic valve gradient by echocardiography was 8.6 ± 4.5 mmHg. Follow up was 100% complete and survival was 99%, 93%, and 89% at one, six, and 12 months, respectively. CONCLUSIONS: Successful outcomes were demonstrated for a VA TAVR program that compared favorably with benchmarks established by the National Transcatheter Valve Therapies Registry. These results provide a necessary transparency of TAVR outcomes at a federal institution.

Ferumoxytol MRA for transcatheter aortic valve replacement planning with renal insufficiency.

BACKGROUND: Computed tomography angiography (CTA) is the test of choice for pre-procedure imaging of transcatheter aortic valve replacement (TAVR) candidates. The iodinated contrast required, however, increases the risk of renal dysfunction in patients with pre-existing renal failure. Ferumoxytol is a magnetic resonance imaging (MRI) contrast agent that can be used with renal failure. Its long vascular resonance time allows gated MRA sequences that approach CTA in image quality. We present respiratory and cardiac gated MRA enabled by ferumoxytol that can be post-processed in an analogous fashion to CTA. METHODS: Seven patients with renal failure presenting for TAVR were imaged with respiratory and cardiac gated MRA at 3T using ferumoxtyol for contrast. Aortic annulus, root and peripheral access dimensions were calculated in a fashion identical to that used for CTA. Of these, 6 patients underwent a TAVR procedure and 5 had intraoperative valve assessment with transesophageal echocardiograph (TEE) using standard clinical protocols that employed both two- and three-dimensional techniques. RESULTS: Good correlation between MRA aortic annulus measurements and those from TEE were shown in 5 patients with mean annulus area of 392.4mm2 (290-470 range) versus 374.1mm2 (285-440 range), with a pairwise correlation coefficient of 0.92, p=0.029. All patients received Sapien valve implants (one 20mm, three 23mm, and two 26mm valves). Access decisions were guided by MRA with no complications. Annulus sizing resulted in no greater than trace/mild aortic regurgitation in all patients. CONCLUSIONS: Ferumoxytol MRA is a safe alternative to CTA in patients with renal failure for pre-TAVR analysis of the aortic root and peripheral access.

The late presenting STEMI: How ECG scores can be used to estimate event time.

INTRODUCTION: Patients presenting with ST elevation myocardial infarction (STEMI) derive significant benefit from timely percutaneous coronary intervention (PCI). Electrocardiogram (ECG) scoring systems can complement history to estimate the infarction age and inform clinical decision-making. CASE: A 76year old man presented with eight days of dyspnea on exertion and chest pain. Triage ECG showed ST elevation and Q waves in the anterior leads. The patient was taken for coronary angiography and found to have a 100% occlusion of the left anterior descending artery. DISCUSSION: Determining timing of acute coronary syndromes is challenging. ECG indices aid clinical history by quantifying infarction acuity.

Risk of contrast-induced nephropathy for patients receiving intravenous vs. intra-arterial iodixanol administration.

PURPOSE: To compare the incidence of contrast-induced nephropathy (CIN) for intravenous vs. intra-arterial administration of iodixanol, compared to non-administration. METHODS: We retrospectively identified 650 patients who had intravenous iodixanol-enhanced CT, 695 with intra-arterial iodixanol cardiac catheterization, 651 with unenhanced CT, and those who also had baseline and follow-up serum creatinine within 5 days of the exam. From the medical records, we recorded the gender, age, baseline and follow-up serum creatinine/eGFR; underlying renal injury risk factors; indication for imaging; contrast material administration volume, concentration, and route of administration; and use of pre-imaging prophylactic measures for CIN. Univariate and multivariate models were used to determine predictors of CIN. RESULTS: Baseline eGFR was lower for patients undergoing unenhanced CT than intravenous or intra-arterial patients (68 vs. 74.6 and 72.2, respectively, p < 0.01) and not different between intravenous and intra-arterial patients (p = 0.735). Simple logistic regression did not show a difference in the rate of CIN in patients who received intravenous vs. intra-arterial iodixanol (28 of 650, 4%, vs. 28 of 695, 4%, respectively, p = 0.798), nor a higher rate of CIN than seen with unenhanced CT (45 of 651, 7%, p = 0.99 and p = 0.98 by one-sided t test). Multivariate regression modeling showed that only elevated baseline creatinine or decreased eGFR and low hematocrit/hemoglobin were associated with CIN incidence (odds ratio 1.28 and 2.5; p < 0.023 and <0.006, respectively). CONCLUSIONS: Elevation in serum creatinine due to intravenous and intra-arterial iodixanol administration is infrequent and is not more common than after unenhanced CT scans.

Development of a Veterans Affairs hybrid operating room for transcatheter aortic valve replacement in the cardiac catheterization laboratory.

IMPORTANCE: Transcatheter aortic valve replacement (TAVR) revolutionized the treatment of aortic stenosis. Developing a TAVR program with a custom-built hybrid operating room (HOR) outside the surgical operating room area poses unique challenges in Veterans Affairs (VA) institutions. OBJECTIVE: To present the process by which the San Francisco VA Medical Center developed a VA-approved TAVR program, in which an HOR exists in a cardiac catheterization laboratory, as a guideline for future programs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of each required approval process for developing an HOR in a cardiac catheterization laboratory in a VA designated for complex surgery. Participants included San Francisco VA Medical Center health care professionals and individuals responsible for new program initiation in VA institutions. EXPOSURES: External reviews by industry vendors, the VA Central Office, and the Office for Construction, Facilities, and Management and an internal Healthcare Failure Mode and Effect Analysis. MAIN OUTCOMES AND MEASURES: The timeline for each process. RESULTS: Developing a TAVR program required vetting and approval from industry vendors, who provided training and expertise. Architectural plans for construction of the HOR began in 2010-2011, followed by approval from Edwards Lifesciences, Inc, in 2012 and fundamentals training on February 8 and 9, 2013. Following a pilot launch of the first VA TAVR program at the Houston VA Medical Center, subsequent programs were required to submit a plan to the VA Central Office for proposed restructuring of their clinical programs. After the San Francisco VA Medical Center proposal submission on February 3, 2013, a site visit consisting of a National Chief of Catheterization Laboratory Managers, a cardiac surgeon, and an interventional cardiologist with TAVR experience was conducted on April 12, 2013. During construction, HOR plans were inspected by the Office for Construction, Facilities, and Management followed by on-site inspection on August 8, 2013, to assess the adequacy of the HOR, newly built restricted corridors, equipment storage areas, and altered staff and patient flow patterns. Last, a Healthcare Failure Mode and Effect Analysis was performed to mitigate any negative effects of the HOR not being colocated in the surgical operating room area. Approval was then granted on November 13, 2013. Our first 10 TAVR cases were successfully completed as of April 2, 2014. CONCLUSIONS AND RELEVANCE: The primary factor for development of a successful TAVR program is integration of the heart valve team. Particular adaptations to the cardiac catheterization laboratory environment are required to accommodate an uncompromised HOR in which cardiac and vascular surgeons can be as comfortable as their interventional cardiology colleagues.

Successful percutaneous management of partial avulsion of the native aortic valve complex complicating transcatheter aortic valve replacement.

This is the first reported case of partial aortic valve and annulus rupture during transcatheter aortic valve replacement, and its successful management through percutaneous means. It stresses the fact that even severe procedural complications can often be treated by a heart team endovascularly, without requiring sternotomy.

High femoral artery bifurcation predicts contralateral high bifurcation: implications for complex percutaneous cardiovascular procedures requiring large caliber and/or dual access.

Recent advances in technology have led to an increase in the use of bilateral femoral artery access and the requirement for large-bore access. Optimal access is in the common femoral artery (CFA), rather than higher (in the external iliac artery) or lower (in one of the branches of the CFA). However, there is a paucity of data in the literature about the relationship between bifurcation level of one CFA and the contralateral CFA. To define the prevalence of high bifurcation of the CFA and the relationship between bifurcation level on both sides, we performed a retrospective analysis of all patients with bilateral femoral angiography. From 4880 femoral angiograms performed at UCSF cardiac catheterization laboratory between 2005-2013, a total of 273 patients had bilateral femoral angiograms. The prevalence of low/normal, high, and very-high femoral bifurcations was 70%, 26%, and 4%, respectively, with no difference between sides. A high or very-high bifurcation significantly increased the likelihood of a high bifurcation on the contralateral side (odds ratio >3.0). Multivariable logistic regression analysis revealed age, gender, self-reported race, height, weight, and body mass index were not predictive of high or very-high bifurcations on either side. In conclusion, high femoral artery bifurcations are common and increase the likelihood of a high bifurcation of the contralateral femoral artery.

Topical nitroglycerin and lidocaine to dilate the radial artery prior to transradial cardiac catheterization: a randomized, placebo-controlled, double-blind clinical trial: the PRE-DILATE Study.

BACKGROUND/OBJECTIVES: Transradial access (TRA) is being increasingly used for both diagnostic and interventional cardiac procedures. Use of TRA offers many advantages: decreased bleeding, vascular complications, reduced length of hospital stay, and reduced cost. However, the small size of the radial artery limits the size of the equipment that can be used via this approach. We sought to determine whether pre-procedural administration of topical nitroglycerin and lidocaine increases the size of the radial artery. METHODS: Patients undergoing transradial cardiac catheterization were randomized in a double-blind fashion to a topical combination of nitroglycerin+lidocaine or placebo ointment. The primary endpoint was change in radial artery size. Secondary endpoints included radial artery spasm and radial artery patency. RESULTS: 86 patients were enrolled (43 allocated to treatment group and 43 to placebo group). Patients underwent ultrasound of the radial artery at baseline and before the catheterization. Complications were rare: one hematoma (placebo group) and one radial artery occlusion (placebo group). Baseline demographic and clinical characteristics were similar. The baseline radial artery cross-sectional area (CSA) was similar in both groups (4.95 ± 0.24 mm(2) in placebo group and 5.14 ± 0.34 mm(2) in the treatment group). However, the final CSA decreased to 4.66 ± 0.25 mm(2) in the placebo group and increased to 5.78 ± 0.38 mm(2) in the treatment group (p=0.02), which corresponded to a decrease in CSA by -5.6 ± 2.1% and an increase in CSA by 16.5 ± 4.2% (p<0.0001), respectively. CONCLUSIONS: Pre-procedural administration of topical mixture of nitroglycerin+lidocaine increases the size of the radial artery in patients undergoing transradial cardiac catheterization. CLINICALTRIALSGOV IDENTIFIER: NCT01155167.

Persistent renal enhancement after intra-arterial versus intravenous iodixanol administration.

PURPOSE: To examine the clinical significance of persistent renal enhancement after iodixanol administration. METHODS: We retrospectively studied 166 consecutive patients who underwent non-enhanced abdominopelvic CT within 7 days after receiving intra-arterial (n=99) or intravenous (n=67) iodixanol. Renal attenuation was measured for each non-enhanced CT scan. Persistent renal enhancement was defined as CT attenuation>55 Hounsfield units (HU). Contrast-induced nephropathy (CIN) was defined as a rise in serum creatinine>0.5 mg/dL within 5 days after contrast administration. RESULTS: While the intensity and frequency of persistent renal enhancement was higher after intra-arterial (mean CT attenuation of 73.7 HU, seen in 54 of 99 patients, or 55%) than intravenous contrast material administration (51.8 HU, seen in 21 of 67, or 31%, p<0.005), a multivariate regression model showed that the independent predictors of persistent renal enhancement were a shorter time interval until the subsequent non-enhanced CT (p<0.001); higher contrast dose (p<0.001); higher baseline serum creatinine (p<0.01); and older age (p<0.05). The route of contrast administration was not a predictor of persistent renal enhancement in this model. Contrast-induced nephropathy was noted in 9 patients who received intra-arterial (9%) versus 3 who received intravenous iodixanol (4%), and was more common in patients with persistent renal enhancement (p<0.01). CONCLUSION: Persistent renal enhancement at follow-up non-contrast CT suggests a greater risk for contrast-induced nephropathy, but the increased frequency of striking renal enhancement in patients who received intra-arterial rather than intravenous contrast material also reflects the larger doses of contrast and shorter time to subsequent follow-up CT scanning for such patients.

Implantation of mouse embryonic stem cell-derived cardiac progenitor cells preserves function of infarcted murine hearts.

Stem cell transplantation holds great promise for the treatment of myocardial infarction injury. We recently described the embryonic stem cell-derived cardiac progenitor cells (CPCs) capable of differentiating into cardiomyocytes, vascular endothelium, and smooth muscle. In this study, we hypothesized that transplanted CPCs will preserve function of the infarcted heart by participating in both muscle replacement and neovascularization. Differentiated CPCs formed functional electromechanical junctions with cardiomyocytes in vitro and conducted action potentials over cm-scale distances. When transplanted into infarcted mouse hearts, CPCs engrafted long-term in the infarct zone and surrounding myocardium without causing teratomas or arrhythmias. The grafted cells differentiated into cross-striated cardiomyocytes forming gap junctions with the host cells, while also contributing to neovascularization. Serial echocardiography and pressure-volume catheterization demonstrated attenuated ventricular dilatation and preserved left ventricular fractional shortening, systolic and diastolic function. Our results demonstrate that CPCs can engraft, differentiate, and preserve the functional output of the infarcted heart.

Comparison between contrast-enhanced magnetic resonance imaging and Selvester QRS scoring system in estimating changes in infarct size between the acute and chronic phases of myocardial infarction.

BACKGROUND: The Selvester QRS score was developed as a method to estimate infarct size (IS) using the ECG and has been validated during the prereperfusion era. Few comparisons exist with contrast-enhanced magnetic resonance imaging (ceMRI) in reperfused patients. This study evaluates the ability of the Selvester QRS score to estimate serial changes in IS during the acute and chronic phases of the infarct evolution in patients who have received reperfusion therapy. METHODS: Thirteen patients with acute myocardial infarction underwent serial ceMRI studies in the acute (<1 week) and chronic phase (>2 months) after their initial myocardial infarction. QRS scoring was performed on the corresponding ECGs. The correlation between ceMRI measurement and QRS score estimation of IS was determined at both time points and for the difference between the two phases. RESULTS: The mean IS was 20.1 +/- 11.0% of total left ventricular mass (% LV) in the acute phase and 13.3 +/- 6.4% LV in the chronic phase ceMRI. The mean IS estimated by Selvester QRS score in the acute and chronic phases were 18.7 +/- 8.2% and 16.4 +/- 8.5% LV, respectively. A modest correlation was found for the acute (r = 0.57) and chronic phase IS (r = 0.54). However, there was no correlation for the difference in IS between the acute and chronic phases. CONCLUSIONS: In this pilot study, the Selvester QRS score correlates modestly to IS by ceMRI during both the acute and chronic phases of the infarction process. The serial changes over time in the Selvester QRS score and IS by ceMRI show no correlation.

Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy.

AIMS: The ability of mesenchymal stem cells (MSCs) to heal the chronically injured heart remains controversial. Here we tested the hypothesis that autologous MSCs can be safely injected into a chronic myocardial infarct scar, reduce its size, and improve ventricular function. METHODS AND RESULTS: Female adult Göttingen swine (n = 15) underwent left anterior descending coronary artery balloon occlusion to create reproducible ischaemia-reperfusion infarctions. Bone-marrow-derived MSCs were isolated and expanded from each animal. Twelve weeks post-myocardial infarction (MI), animals were randomized to receive surgical injection of either phosphate buffered saline (placebo, n = 6), 20 million (low dose, n = 3), or 200 million (high dose, n = 6) autologous MSCs in the infarct and border zone. Injections were administered to the beating heart via left anterior thoracotomy. Serial cardiac magnetic resonance imaging was performed to evaluate infarct size, myocardial blood flow (MBF), and left ventricular (LV) function. There was no difference in mortality, post-injection arrhythmias, cardiac enzyme release, or systemic inflammatory markers between groups. Whereas MI size remained constant in placebo and exhibited a trend towards reduction in low dose, high-dose MSC therapy reduced infarct size from 18.2 +/- 0.9 to 14.4 +/- 1.0% (P = 0.02) of LV mass. In addition, both low and high-dose treatments increased regional contractility and MBF in both infarct and border zones. Ectopic tissue formation was not observed with MSCs. CONCLUSION: Together these data demonstrate that autologous MSCs can be safely delivered in an adult heart failure model, producing substantial structural and functional reverse remodelling. These findings demonstrate the safety and efficacy of autologous MSC therapy and support clinical trials of MSC therapy in patients with chronic ischaemic cardiomyopathy.