Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients.

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre-formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%-97%) and 6250 (5000-10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14-0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037.

The effects of donor-specific antibody characteristics on cardiac allograft vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) causes late graft dysfunction and post-transplant mortality. Currently, the effects of different donor-specific antibodies (DSA) on the severity of CAV remain unclear. METHOD: We evaluated 526 adult heart transplant recipients at a single center between January 2010 and August 2015. Subjects were divided into those with DSA (n = 142) and those without DSA (n = 384, control). The DSA group was stratified into persistent DSA (n = 34), transient DSA (n = 105), 1:8 dilution DSA (n = 45), complement-binding (C1q) DSA (n = 36), Class I DSA (n = 37), and Class II DSA (n = 105). The primary outcome was the incidence of moderate-to-severe CAV (CAV 2/3) at 5-year follow-up. RESULTS: Subjects with persistent DSA, 1:8 dilution DSA, and C1q DSA had higher incidence of CAV 2/3 compared the control group (17.6%, 13.3%, and 16.7% vs. 3.1%, respectively; P≤ .001). The incidence of CAV 2/3 between subjects with transient DSA and the control group was similar (2.8% vs. 3.1%; P = .888). Subjects with Class II DSA also had higher incidence of CAV 2/3 (7.6% vs. 3.1%; P = .039). CONCLUSION: DSA that are persistent, 1:8 dilution positive, C1q positive, and Class II are associated with more severe grades of CAV. These DSA characteristics may prognosticate disease and warrant consideration for treatment.

Coronary Vascular Function and Cardiomyocyte Injury: A Report From the WISE-CVD.

OBJECTIVE: Women with symptoms or signs of myocardial ischemia but no obstructive coronary artery disease (INOCA) often have coronary vascular dysfunction and elevated risk for adverse cardiovascular events. We hypothesized that u-hscTnI (ultra-high-sensitivity cardiac troponin I), a sensitive indicator of ischemic cardiomyocyte injury, is associated with coronary vascular dysfunction in women with INOCA. Approach and Results: Women (N=263) with INOCA enrolled in the WISE-CVD study (Women's Ischemic Syndrome Evaluation-Coronary Vascular Dysfunction) underwent invasive coronary vascular function testing and u-hscTnI measurements (Simoa HD-1 Analyzer; Quanterix Corporation, Lexington, MA). Logistic regression models, adjusted for traditional cardiovascular risk factors were used to evaluate associations between u-hscTnI and coronary vascular function. Women with coronary vascular dysfunction (microvascular constriction and limited coronary epicardial dilation) had higher plasma u-hscTnI levels (both P=0.001). u-hscTnI levels were associated with microvascular constriction (odds ratio, 1.38 per doubling of u-hscTnI [95% CI, 1.03-1.84]; P=0.033) and limited coronary epicardial dilation (odds ratio, 1.37 per doubling of u-hscTnI [95% CI, 1.04-1.81]; P=0.026). u-hscTnI levels were not associated with microvascular dilation or coronary epicardial constriction. CONCLUSIONS: Our findings indicate that higher u-hscTnI is associated with coronary vascular dysfunction in women with INOCA. This suggests that ischemic cardiomyocyte injury in the setting of coronary vascular dysfunction has the potential to contribute to adverse cardiovascular outcomes observed in these women. Additional studies are needed to confirm and investigate mechanisms underlying these findings in INOCA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00832702.

Coronary computed tomography-angiography quantitative plaque analysis improves detection of early cardiac allograft vasculopathy: A pilot study.

Cardiac allograft vasculopathy (CAV) is an increasingly important complication after cardiac transplant. We assessed the additive diagnostic benefit of quantitative plaque analysis in patients undergoing coronary computed tomography-angiography (CCTA). Consecutive patients undergoing CCTA for CAV surveillance were identified. Scans were visually interpreted for coronary stenosis. Semiautomated software was used to quantify noncalcified plaque (NCP), as well as its components. Optimal diagnostic cut-offs for CAV, with coronary angiography as gold standard, were defined using receiver operating characteristic curves. In total, 36 scans were identified in 17 patients. CAV was present in 17 (46.0%) reference coronary angiograms, at a median of 1.9 years before CCTA. Median NCP (147 vs 58, P < .001), low-density NCP (median 4.5 vs 0.9, P = .003), fibrous plaque (median 76.1 vs 31.1, P = .003), and fibrofatty plaque (median 63.6 vs 27.6, P < .001) volumes were higher in patients with CAV, whereas calcified plaque was not (median 0.0 vs 0.0, P = .510). Visual assessment of CCTA alone was 70.6% sensitive and 100% specific for CAV. The addition of total NCP volume increased sensitivity to 82.4% while maintaining 100% specificity. NCP volume is significantly higher in patients with CAV. The addition of quantitative analysis to visual interpretation improves the sensitivity for detecting CAV without reducing specificity.

High thrombus burden despite thrombolytic therapy in ST-elevation myocardial infarction in a patient with COVID-19.

Consideration of thrombolysis as first-line reperfusion therapy in patients with COVID-19 and STEMI is recommended by ACC/SCAI guidelines. We describe a patient with COVID-19, who presented with ST-elevation myocardial infarction and was treated with thrombolysis and anticoagulation. He was later found to have a significant persistent thrombus burden requiring thrombectomy and stent placement. Invasive hemodynamics on multiple high-dose pressers revealed a high cardiac output state with low systemic vascular resistance, consistent with distributive rather than cardiogenic shock. Our case illustrates that thrombolytic therapy alone may not be adequate in patients with STEMI and COVID-19, as well as the importance of early invasive hemodynamics in management of shock in patient with STEMI and COVID-19 infection.

Prevalence of Coronary Endothelial and Microvascular Dysfunction in Women with Symptoms of Ischemia and No Obstructive Coronary Artery Disease Is Confirmed by a New Cohort: The NHLBI-Sponsored Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD).

OBJECTIVE: In a separate, contemporary cohort, we sought to confirm findings of the original Women's Ischemia Syndrome Evaluation (WISE). BACKGROUND: The original WISE observed a high prevalence of both invasively determined coronary endothelial and coronary microvascular dysfunction (CMD) that predicted adverse events in follow-up. METHODS: We comparatively studied the WISE-Coronary Vascular Dysfunction (CVD) cohort (2009-2011), with signs and symptoms of ischemia but without significant CAD, to the original WISE (1997-2001) cohort. CMD was defined as coronary flow reserve (CFR) ≤2.5, or endothelial dysfunction as epicardial coronary artery constriction to acetylcholine (ACH), or <20% epicardial coronary dilation to nitroglycerin (NTG). RESULTS: In WISE (n=181) and WISE-CVD (n=235) women, mean age in both was 54 years, and 83% were white (WISE) vs 74% (WISE-CVD, p=0.04). Use of hormone replacement therapy was less frequent in WISE-CVD vs WISE (46% vs 57%, p=0.026) as was presence of hypertension (40% vs 52%, p=0.013), hyperlipidemia (20% vs 46%, p<0.0001), and smoking (46% vs 56%, p=0.036). Similar rates were observed in WISE-CVD and WISE cohorts for CMD (mean CFR 2.7±0.6 vs 2.6±0.8, p=0.35), mean change in diameter with intracoronary ACH (0.2±10.0 vs 1.6±12.8 mm, p=0.34), and mean change in diameter with intracoronary NTG (9.7±13.0 vs 9.8±13.5 mm, p=0.94), respectively. CONCLUSIONS: This study confirms prevalence of CMD in the contemporary WISE-CVD cohort similar to that of the original WISE cohort, despite a lower risk factor burden in WISE-CVD. Because these coronary functional abnormalities predict major adverse cardiac events, clinical trials of therapies targeting these abnormalities are indicated.

Does ex vivo perfusion lead to more or less intimal thickening in the first-year post-heart transplantation?

BACKGROUND: The Organ Care System (OCS), an ex vivo heart perfusion platform, represents an alternative to the current standard of cold organ storage that sustains the donor heart in a near-physiologic state. Previous reports showed that this system had significantly shortened the cold ischemic time from standard cold storage (CS). However, the effect of reduced ischemic injury against the coronary vascular bed has not been examined by intravascular ultrasound (IVUS). METHODS: Between August 2011 and February 2013, heart transplant (HTx) candidates enrolled in the PROCEED 2 trial were randomized to either CS or OCS. IVUS was performed at 4-6 weeks (baseline) and repeated 1 year after transplantation. The change in maximal intimal thickness (MIT) and other clinical outcomes were examined. RESULTS: Thirty-nine patients were randomized and underwent HTx by OCS (n=16) or CS (n=18). Of these, 18 patients (OCS: n=5, CS: n=13) with paired IVUS were examined. There were no significant differences in the change of MIT and other clinical outcomes between the groups. CONCLUSION: The incidence of cardiac allograft vasculopathy in donor hearts preserved with the OCS versus CS was similar. These results suggest that this ex vivo allograft perfusion system is a promising and valid platform for donor heart transportation.

Long-term clinical and angiographic outcomes of percutanenous coronary intervention with everolimus-eluting stents for the treatment of cardiac allograft vasculopathy.

BACKGROUND: Percutaneous coronary intervention (PCI) with bare-metal and first-generation drug-eluting stents (DES) for cardiac allograft vasculopathy (CAV) is associated with unexpectedly high restenosis rates and target lesion revascularization (TLR). Long-term outcomes of stenting for CAV using second-generation everolimus-eluting stents (EES) are not established. OBJECTIVE: To evaluate clinical and angiographic outcomes of CAV stenting with EES. METHODS: Patients who underwent PCI with EES for CAV were studied. Surveillance angiography was performed at 6-12 months post-PCI and as indicated. Patient survival, freedom from MACE, binary restenosis, TLR, target vessel revascularization (TVR), and non-TVR are reported. RESULTS: One-hundred and thirty two EES were placed in 113 discrete lesions in 48 patients. Pre-PCI stenosis was 82.1 ± 12.4%, and average stent length and diameter were 16.9 ± 5.7 and 3.0 ± 0.6 mm, respectively. Mean follow-up was 30.7 ± 18.8 months. Time from transplantation to PCI was 9.9 ± 5.1 years. Post-PCI survival at 1 (93.5 ± 3.6%), 2 (91.0 ± 4.3%), and 3 years (83.8 ± 6.3%), and freedom from MACE (87.2 ± 4.9%, 82.3 ± 5.7%, 75.8 ± 6.9%) were high. Binary restenosis at 1 (3.0 ± 1.7%), 2 (6.9 ± 3.2%), and 3 years (10.0 ± 4.3%) mirrored expected rates with EES use in native CAD. One-, two-, and three-year rates of TLR (5.1 ± 2.5%, 14.3 ± 4.6%, and 21.2 ± 6.3%), TVR (17.1 ± 4.5%, 39.0 ± 6.9%, and 46.2 ± 7.8%), and NTVR (26.3 ± 5.4%, 55.4 ± 7.0%, and 58.0 ± 7.0%) remain high. Diabetes was associated with an increased hazard ratio for binary restenosis 6.084 (95% CI 1.271-29.133, P = 0.024). CONCLUSIONS: PCI strategy using EES in the treatment of CAV was associated with a low binary restenosis rate, a high survival rate, and a high rate of freedom from MACE. However, at 3 years, TLR and TVR rates appeared similar to rates observed with first-generation DES. © 2016 Wiley Periodicals, Inc.

Angiogenesis on coronary angiography is a marker for accelerated cardiac allograft vasculopathy as assessed by intravascular ultrasound.

BACKGROUND: Errant neovascularization and coronary artery fistulae (CAF) are frequently observed after cardiac transplantation. The relationship between angiographic neovascularization/CAF and coronary plaque progression is unknown. METHODS: Angiography and intravascular ultrasound were routinely performed at 4-6 weeks and 1-year post-transplant. Pts were divided into three groups: no angiographic angiogenesis (Group 1), neovascularization only (Group 2), and CAF (Group 3). First-year changes in maximal intimal thickness (MIT), maximal intimal area (MIA), and percent atheroma volume (PAV) were compared between groups. RESULTS: The 106 pts were included, 40/106 in Group 1, 42/106 in Group 2, and 24/106 in Group 3. Respectively, first-year ΔMIT was 0.14 ± 0.13 mm, 0.32 ± 0.26 mm, and 0.50 ± 0.34 mm, P < .001. ΔMIA was 0.6 ± 0.6 mm2 , 1.7 ± 1.8 mm2 , and 3.0 ± 2.6 mm2 , P < .001. ΔPAV was 2.3 ± 2.5%, 6.0 ± 5.1%, and 9.6 ± 9.0%, P < .001. Rapid plaque progression occurred in 1/40 (2.5%) pts in Group 1, 12/42 (28.6%) in Group 2, and 12/24 (50%) in Group 3, P < .001. Multivariate analysis identified both antithymocyte globulin and presence of CAF as independently associated with rapid plaque progression: OR 0.29 (P = .038) and 4.04 (P = .014). CONCLUSION: Neovascularization and CAF are commonly present on surveillance angiography after cardiac transplantation and may signify amplified angiogenesis. Their presence is associated with accelerated coronary plaque progression by IVUS.

Device Strategies for Patients in INTERMACS Profiles 1 and 2 Cardiogenic Shock: Double Bridge With Extracorporeal Membrane Oxygenation and Initial Implant of More Durable Devices.

For Interagency Registry for Mechanically Assisted Circulatory Support profiles 1 and 2 cardiogenic shock patients initially placed on extracorporeal membrane oxygenation (ECMO), whether crossover to more durable devices is associated with increased survival, and its optimal timing, are not established. Profiles 1 and 2 patients placed on mechanical support were prospectively registered. Survival and successful hospital discharge were compared between patients placed on ECMO only, ECMO with early crossover, and ECMO with delayed crossover. Survival of patients directly implanted with non-ECMO devices was also reported. One-hundred and sixty-two patients were included. Mean age was 52.2 ± 13.8 years. Seventy-three of 162 (45.1%) were initiated on ECMO. Of these, 43 were supported with ECMO only, 11 were crossed-over early <4 days, and 19 were crossed-over in a delayed fashion. Survival was different across groups (Log-rank P < 0.002). In multivariate analysis, early crossover was associated with decreased mortality as compared with no crossover (hazard ratio [HR] 0.201, 95% confidence interval [95%CI] 0.058-0.697, P = 0.011) or with delayed crossover (HR 0.255, 95%CI 0.073-0.894, P = 0.033). Mortality was not different between delayed crossover and no crossover (P = 0.473). In patients with early crossover there were no deaths at 30 days, and 60-day survival was 90.0 ± 9.5%. Survival to hospital discharge was 72.8%. For patients directly implanted with non-ECMO devices, 30-day and 60-day survival was 90.9 ± 3.1% and 87.3 ± 3.8%, respectively, and survival to hospital discharge was 78.7%. Both initial implant of durable devices and double bridge strategy was associated with improved outcomes. If the double bridge strategy is chosen, early crossover is associated with improved survival and successful hospital discharge.

Tricuspid Regurgitation, the Forgotten Valvular Lesion-A Contemporary Review of Etiology, Prevalence, and Management Options.

Tricuspid regurgitation (TR) is a common finding. Pathologic TR is an independent risk factor for mortality. TR can be classified by etiology into functional versus organic. Organic TR is caused by structural damage to the tricuspid valve (TV) by a spectrum of etiologies, including pacemaker leads and right heart biopsies, whereas functional TR is predominantly due to elevated pulmonary pressures. Atrial fibrillation and chamber enlargement, among other risk factors, are strong predictors of functional TR. Correction of elevated pulmonary pressures improves TR, and concurrent repair of severe TR at the time of left heart valve surgery improves postoperative heart failure symptoms but does not improve survival. TR repair is associated with less operative and long-term mortality than TV replacement, and demonstrates similar improvements in heart failure symptoms. Substantial residual TR remains after repair, and reoperative mortality for residual TR is considerable. Percutaneous TV replacement may offer a rescue strategy.

Elevated immune monitoring early after cardiac transplantation is associated with increased plaque progression by intravascular ultrasound.

BACKGROUND: Immune monitoring (IM) has not been shown to be associated with cardiac allograft vasculopathy (CAV). METHODS: Maximal intimal area, average percent stenosis, plaque volume, and maximal intimal thickness (MIT) were measured for matched baseline and one-yr IVUS segments in a blinded fashion. Patients were divided into quartiles by IM scores and outcomes compared. Optimal IM cutoff was determined. RESULTS: IM assays were measured at 63.7 ± 16.4 d after transplantation in fifty patients. Progression of maximal intimal area (p = 0.005), average percent stenosis (p < 0.001), plaque volume (p = 0.005), and MIT (p = 0.001) were increased across the quartiles. An optimal IM assay cutoff of 406.0 ng ATP/mL demonstrated a sensitivity of 66.7% and specificity of 94.3% for predicting rapid progression of MIT ≥ 0.5 mm. Mean IM scores for Group 1 vs. Group 2 were 176.4 ± 102.2 and 616.3 ± 239.5 ngATP/mL, respectively. Rapid progression of MIT ≥ 0.5 mm occurred in 5/38 patients (13.2%) in Group 1 vs. 10/12 patients (83.3%) in Group 2 (p < 0.001). The risk ratio for rapid progression with elevated IM was 11.7 (p < 0.001). CONCLUSION: Elevated early IM scores are associated with progression of CAV by IVUS. These findings suggest the potential of IM for tailoring of immunosuppressive regimens to minimize the progression of CAV in high-risk patients.

Clinical outcomes in fulminant myocarditis requiring extracorporeal membrane oxygenation: a weighted meta-analysis of 170 patients.

BACKGROUND: Fulminant myocarditis (FM) is often a self-resolving entity if the patient survives the acute illness. Venoarterial extracorporeal membrane oxygenation (ECMO) has been used successfully for treatment of cardiogenic shock or cardiac arrest due to FM. However, clinical outcomes are not well understood, in part because of small study sizes. In the absence of large clinical trials, performance of pooled analysis represents the best method for ascertaining survival rates for ECMO. METHODS: A systematic Medline search was conducted on ECMO for the treatment of FM, updated up to November 2012. Studies with n ≥10 published in the year 2000 or later that reported survival to hospital discharge for FM requiring ECMO were included. Studies that reported only on pediatric patients were excluded. The smaller of studies with overlapping patients were excluded. Cochran Q and I(2) were calculated and reported. RESULTS: Six studies were included in the analysis, encompassing 170 patients. The minimum and maximum reported rates of survival to hospital discharge were 60.0% and 87.5%, respectively. The cumulative rate was 115/170. The calculated Cochran Q value was 3.63, which was not significant for heterogeneity. The I(2) value was 0%. The pooled estimate rate was 66.9% with a 95% confidence interval of 59.4%-73.7%. CONCLUSION: More than two-thirds of patients with FM and either cardiogenic shock and/or cardiac arrest survive to hospital discharge with ECMO. These findings could be used in the risk-benefit analysis when initiation of a cardiopulmonary bypass system is being considered for FM.

Clinical and angiographic outcomes with everolimus eluting stents for the treatment of cardiac allograft vasculopathy.

OBJECTIVES: This study aimed to examine clinical efficacy, safety, and intermediate clinical outcomes with everolimus-eluting stents (EESs) in patients with transplant coronary artery disease (TCAD). BACKGROUND: TCAD is a major cause of mortality in patients following orthotopic heart transplantation (OHT). Systemic everolimus in OHT patients has been shown to reduce TCAD. The safety and efficacy of an EES, the Xience V, have not been evaluated in this population. METHODS: Patients post-OHT with hemodynamically significant CAD who underwent percutaneous coronary intervention (PCI) with EES were included. Participants were maintained on dual antiplatelet therapy for 1-year post-PCI. We examined procedural success, in-hospital and 1-year mortality, stent thrombosis, angiographic restenosis, and myocardial infarction rates. All patients had follow-up angiography 1-year after PCI. Target vessel revascularization (TVR), target lesion revascularization (TLR), in-segment restenosis, target vessel failure (TVF), and lumen late loss were noted. RESULTS: PCI was performed in 34 de novo lesions in 21 patients, and 40 EES were placed. Procedural success rate was 100%. Average stent was 16.5 ± 5.1 mm long and 3.0 ± 0.6 mm in diameter. All patients had angiographic follow-up (409 ± 201 days). There was no stent thrombosis, deaths, or myocardial infarctions during follow-up. Two patients had focal in-stent restenosis. TLR rate was 5.9% (2/34), and TVR rate was 11.1% (3/27). Quantitative coronary angiography (QCA) showed stenosis diameter to be 19.98 ± 17.57%. CONCLUSIONS: Use of an EES is associated with a low incidence of TVR and TLR in patients with TCAD. Further studies are needed to determine whether PCI with EES changes long-term outcomes.

Ten-year follow-up cohort of the everolimus versus azathioprine multinational prospective study focusing on intravascular ultrasound findings.

BACKGROUND: Long-term clinical outcomes of early intravascular ultrasound (IVUS) findings in a prospective cohort of heart transplantation (HTx) patients have not been evaluated. METHODS: This study included patients from 20 centers across Europe and North and South America among the original cohort of the RAD B253 study. Among these patients, 91 had paired IVUS images at baseline and 1-year post-transplant: everolimus 1.5 mg group (n = 25), everolimus 1.5 mg group (n = 33), and azathioprine 3.0 group (n = 33). The primary outcome was a composite of cardiovascular death, retransplantation, myocardial infarction (MI), coronary revascularization, and cardiac allograft vasculopathy (CAV) within a 10-year follow-up period. The secondary outcome was all-cause death, cardiovascular death, retransplantation, MI, coronary revascularization, and CAV. Donor disease was defined as baseline maximal intimal thickness (MIT) >0.66 mm, and rapid progression was defined as a change in MIT > 0.59 mm at 1 year. RESULTS: Donor disease (46 patients) was associated with a higher incidence of the primary outcome (hazard ratio (HR) 4.444, 95% confidence interval [CI] 1.946-10.146, p < 0.001). Rapid progression (44 patients) was associated with a significantly higher incidence of the primary outcome (HR 2.942, 95% CI 1.383-6.260, p = 0.005). Higher-risk features on IVUS (positive both donor disease and rapid progression) were independently associated with poor clinical outcomes (HR 4.800, 95% CI 1.816-12.684, p = 0.002). CONCLUSIONS: An increase in baseline MIT and a change in first-year MIT in IVUS post HTx was associated with poor outcomes up to 10 years. Early IVUS findings can be considered as surrogate endpoints for evaluating long-term outcomes in HTx clinical trials.

Change in First-year Intravascular Ultrasound Results Predicts Adverse Events in Heart Transplant Recipients: Implications for Clinical Trial Endpoints.

BACKGROUND: Heart transplantation (HTx) is an established therapeutic option for patients with advanced heart failure who are refractory to conventional guideline-directed treatments. This study aimed to reassess whether intravascular ultrasound variables could predict adverse events after HTx in the modern era. METHODS: One hundred primary HTx recipients with available serial intravascular ultrasound examination results of the left anterior descending artery 4-8 wk and 1 y after HTx were enrolled, with an average follow-up duration of 5.7 y. The primary endpoint was a composite of all-cause death, nonfatal major adverse cardiac events, and angiographic cardiac allograft vasculopathy. RESULTS: Forty-three patients developed primary endpoints. The baseline maximal intimal thickness was independently associated with the primary endpoint (hazard ratio, 8.24; 95% confidential interval [CI], 3.21-21.21; P < 0.001), and the optimal cutoff value was 0.64 mm. A change in the plaque atheroma volume in a proximal 20-mm segment from the left anterior descending artery bifurcation >1.05 mm 3 /mm (hazard ratio, 2.75; 95% CI, 1.28-5.89; P = 0.009) and a change in the first-year maximal intimal thickness >0.27 mm (hazard ratio, 2.63; 95% CI, 1.05-6.56; P = 0.04) were independent predictors of the primary endpoint 1 y after intravascular ultrasonography. CONCLUSIONS: The aforementioned important clinical implications of intravascular ultrasound parameters are useful predictors of outcomes, which may be considered endpoints in modern clinical HTx trials.

Case report: Repeat coronary function testing in women with ischemia and no obstructive coronary artery disease.

Women with signs and symptoms of ischemia and no obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD). It can be diagnosed by coronary function testing (CFT), which is an invasive coronary angiogram procedure. Frequently, these women have persistent angina despite medical therapy, but it is not clear whether it is due to worsening or persistent CMD or inadequate therapy. In this brief report, we describe findings of repeat CFT in a case series of 12 women undergoing repeat CFT for the assessment of persistent angina in order to better understand the evolving pathology.

Feasibility and safety of percutaneous coronary intervention in patients with end-stage liver disease referred for liver transplantation.

Percutaneous coronary intervention (PCI) has traditionally not been an option for patients with end-stage liver disease (ESLD) and coronary artery disease (CAD). This retrospective study was designed to demonstrate the feasibility and safety of PCI in liver transplant candidates. Patients with ESLD and hemodynamically significant CAD who were otherwise deemed to be acceptable candidates for liver transplantation underwent PCI. The procedural success rates, mortality and myocardial infarction rates, and bleeding outcomes were examined. Sixteen patients with ESLD underwent PCI: 15 with bare-metal stents (1.3 stents per patient on average) and 1 with balloon angioplasty alone. The median diameter stenosis per lesion was 80%, the median platelet count was 68 × 10(9) /L, the median international normalized ratio was 1.3, and the median Model for End-Stage Liver Disease score was 13. PCI was successful in 94% of the patients. One patient had a suboptimal residual stenosis of 50% after stenting. There were no in-hospital or 30-day deaths or myocardial infarctions, and no patients developed hematomas. One patient required a 1-U platelet transfusion, and another required 1 U of packed red blood cells. All patients remained clinically stable 1 month after PCI. Nine of the 16 patients were listed for liver transplantation, and 3 patients underwent liver transplantation. In conclusion, we have demonstrated the safety and feasibility of PCI in a small cohort of patients with ESLD and hemodynamically significant CAD, the majority of whom had significant thrombocytopenia. Larger studies are required to determine whether PCI is an effective treatment strategy for patients with ESLD and hemodynamically significant CAD who otherwise would not be candidates for liver transplantation.

Coronary microvascular dysfunction: Considerations for diagnosis and treatment.

Ischemia and no obstructive coronary artery disease (INOCA) is an increasingly recognized cause of angina, and it is more commonly diagnosed in women. Coronary microvascular dysfunction (CMD), or the abnormal dilation and constriction of the small vessels of the heart, is the underlying cause of INOCA in one-half of cases. This review discusses coronary microvascular pathophysiology, considerations for invasive coronary function testing and noninvasive diagnostic modalities, implications for management, and remaining knowledge gaps.

Heart Transplantation for Giant Cell Myocarditis: A Case Series.

BACKGROUND: Giant cell myocarditis (GCM) has a poor prognosis without heart transplant, but post-transplant survival is unknown. PURPOSE: To describe the post-transplant survival of patients with GCM at a large transplant center. METHODS: Seven patients underwent heart transplant for histologically confirmed GCM of the explanted heart. The median age was 59 years, and 43% (3 of 7) were female. All patients had cardiogenic shock, multiorgan failure, elevated troponin, and recurrent ventricular tachycardia, and some required mechanical circulatory support. All patients received rabbit antithymocyte globulin (rATG) in the perioperative period at a dose of 1.5 mg/kg daily for 1 to 5 days and 4 received intravenous immunoglobulin 1 g/kg daily for 2 days after rATG. All patients had early initiation of tacrolimus by first to third postoperative day depending on renal function, early mycophenolate, and high dose steroid. All were maintained using tacrolimus, mycophenolate, and prednisone. RESULTS: One patient had asymptomatic recurrence of GCM at 3 months, managed by up-titration of tacrolimus, and had asymptomatic 2R cellular rejection at 4 months, managed with steroid bolus. No patient had high-grade rejection. One patient died at 267 days, possibly of GCM. Six of 7 (86%) remain alive at a median of 842 days (2.3 years) post transplant. CONCLUSIONS: Patients with GCM have excellent post-transplant survival with use of rATG and triple drug immunosuppressive therapy; however, some patients remain at risk for GCM recurrence after transplant, which may respond to augmented immunosuppression.