Genetically Modified Porcine-to-Human Cardiac Xenotransplantation.

A 57-year-old man with nonischemic cardiomyopathy who was dependent on venoarterial extracorporeal membrane oxygenation (ECMO) and was not a candidate for standard therapeutics, including a traditional allograft, received a heart from a genetically modified pig source animal that had 10 individual gene edits. Immunosuppression was based on CD40 blockade. The patient was weaned from ECMO, and the xenograft functioned normally without apparent rejection. Sudden diastolic thickening and failure of the xenograft occurred on day 49 after transplantation, and life support was withdrawn on day 60. On autopsy, the xenograft was found to be edematous, having nearly doubled in weight. Histologic examination revealed scattered myocyte necrosis, interstitial edema, and red-cell extravasation, without evidence of microvascular thrombosis - findings that were not consistent with typical rejection. Studies are under way to identify the mechanisms responsible for these changes. (Funded by the University of Maryland Medical Center and School of Medicine.).

Sexual Quality of Life in Left Ventricular Assist Device Patients and Their Partners.

BACKGROUND: Living with a left ventricular assist device (LVAD) comes with potentially burdensome aspects posed by, for example, battery packs and device drivelines. We aim to describe the impact of living with a durable LVAD on sexual quality of life (QOL), depression, and anxiety in patients and their partners. METHODS AND RESULTS: In this single-center, prospective, observational study, patients ≥4 months after LVAD implantation and their partners completed the Sexual Activities in Left Ventricular Assist Device Patients or Partners questionnaire to assess their sexual QOL, the 8-item Patient Health Questionnaire (PHQ-8) to assess symptoms of depression and the 7-item Generalized Anxiety Disorder (GAD-7) to assess symptoms of anxiety. Sixty patients and 60 partners completed the questionnaires 2.3 ± 1.9 years after implantation. Eighty-seven percent of the patients and 13% of partners were male. The mean age of patients was 57.4 ± 13.3 years, with 90% living with their partner. Ten percent of patients and 18% of partners had a current diagnosis of a psychological condition, most frequently depression and/or anxiety. Overall, 49% of participants indicated the LVAD influenced their sexual activity (patients 53% vs partners 45%; P = .33). Disturbances from the driveline were the most common problem indicated. Twenty-four percent of participants had scored in the mild to moderate depression range on the PHQ-8 and 28% scored in the mild to severe anxiety range on the GAD-7. The median total GAD-7 (1 [interquartile range (IQR) 0-4.25] vs 2.5 [IQR 0-5]; P = .06) were comparable between patients and partners; whereas patients had a higher total PHQ-8 score (3 [IQR 0-5.25] vs 1 [IQR 0-3.25]; P = .02). A preference to receive information regarding sexuality while on LVAD support was indicated by 54% of participants and did not differ between patients and partners (P > .99). Written resources were the most commonly preferred source of information. CONCLUSIONS: LVADs severely affect the sexual QOL for patients and their partners. The presence of a driveline is a major cause for concern. Patients prefer receiving written information on how to improve their sexual QOL.

Transcatheter Left Ventricular Restoration in Patients With Heart Failure.

BACKGROUND: Left ventricular (LV) volume reshaping reduces myocardial wall stress and may induce reverse remodeling in patients with heart failure with reduced ejection fraction. The AccuCinch Transcatheter Left Ventricular Restoration system consists of a series of anchors connected by a cable implanted along the LV base that is cinched to the basal free wall radius. We evaluated the echocardiographic and clinical outcomes following transcatheter left ventricular restoration. METHODS AND RESULTS: We analyzed 51 heart failure patients with a left ventricular ejection fraction between 20% and 40%, with no more than 2+ mitral regurgitation treated with optimal medical therapy, who subsequently underwent transcatheter left ventricular restoration. Serial echocardiograms, Kansas City Cardiomyopathy Questionnaire scores, and 6-minute walk test distances were measured at baseline through 12 months. Primary analysis end point was change in end-diastolic volume at 12 months compared with baseline. Patients (n = 51) were predominantly male (86%) with a mean age of 56.3 ± 13.1 years. Fluoroscopy showed LV free wall radius decreased by a median of 9.2 mm amounting to a 29.6% decrease in the free wall arc length. At 12 months, the LV end-diastolic volume decreased by 33.6 ± 34.8 mL (P < .01), with comparable decreases in the LV end-systolic volume. These decreases were associated with significant improvements in the overall Kansas City Cardiomyopathy Questionnaire score (16.4 ± 18.7 points; P < .01) and 6-minute hall walk test distance (45.9 ± 83.9 m; P < .01). There were no periprocedural deaths; through the 1-year follow-up, 1 patient died (day 280) and 1 patient received a left ventricular assist device (day 13). CONCLUSIONS: In patients with heart failure with reduced ejection fraction without significant mitral regurgitation receiving optimal medical therapy, the AccuCinch System resulted in decreases of LV volume, as well as improved quality of life and exercise endurance. A randomized trial is ongoing (NCT04331769).

Urinary Cell-Cycle Arrest Biomarkers as Early Predictors of Acute Kidney Injury After Ventricular Assist Device Implantation or Cardiac Transplantation.

OBJECTIVES: Acute kidney injury (AKI) remains a leading source of morbidity and mortality after cardiothoracic surgery. Insulin-like growth factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinases-2 (TIMP-2), are novel early-phase renal biomarkers that have been validated as sensitive predictors of AKI. Here the authors studied the efficacy of these biomarkers for predicting AKI after left ventricular assist device (LVAD) implantation and cardiac transplantation. DESIGN/SETTING/PARTICIPANTS/INTERVENTIONS: This was a prospective study of 73 patients undergoing LVAD implantation (n = 37) or heart transplant (n = 36) from 2016 to 2017 at the authors' center. TIMP-2 and IGFBP7 were measured with the NephroCheck Test on urine samples before surgery and one-to-six hours after surgery. NephroCheck scores were assessed as predictors of moderate/severe AKI (Kidney Disease International Global Outcomes 2/3 creatinine criteria) within 48 hours of surgery, and the association with survival to one year was investigated. MEASUREMENTS AND MAIN RESULTS: The LVAD and transplant cohorts overall were similar in demographics and baseline creatinine (p > 0.05), with the exception of having more African-American patients in the LVAD arm (p = 0.003). Eleven (30%) LVAD and 16 (44%) transplant patients developed moderate/severe AKI. Overall, AKI was associated with postsurgery NephroCheck (odds ratio [95% confidence interval] for 0.1 mg/dL increase: 1.36 [1.04-1.79]; p = 0.03), but not with baseline NephroCheck (p = 0.92). When analyzed by cohort, this effect remained for LVAD (1.68 [1.05-2.71]; p = 0.03) but not for transplant (p = 0.15). Receiver operating characteristic analysis showed postoperative NephroCheck to be superior to baseline creatinine in LVAD (p = 0.046). Furthermore, an increase of 0.1 mg/dL in postoperative NephroCheck was associated with a 10% increase in the risk of mortality (adjusted hazard ratio: 1.11 [1.01-1.21]; p = 0.04) independent of age and body mass index. CONCLUSION: Assessment of TIMP-2 and IGFBP7 within six hours after surgery appeared effective at predicting AKI in patients with LVADs. Larger studies are warranted to validate these findings.

Health-Related Quality of Life in Patients With a Left Ventricular Assist Device (QOLVAD) Questionnaire: Initial Psychometrics of a New Instrument.

BACKGROUND: Patients with a left ventricular assist device are a unique and growing population who deserve their own valid, reliable instrument for health-related quality of life. OBJECTIVE: We developed and tested the Health-Related Quality of Life with a Left Ventricular Assist Device (QOLVAD) questionnaire. METHODS: In a prospective, descriptive study, patients from 7 sites completed the QOLVAD and comparator questionnaires. Construct validity was tested using confirmatory factor analysis. Convergent validity was tested using correlations of QOLVAD scores to well-established measures of subjective health status, depression, anxiety, and meaning/faith. Reliability and test-retest reliability were quantified. RESULTS: Patients (n = 213) were 58.7 ± 13.9 years old; 81.0% were male, 73.7% were White, and 48.0% had bridge to transplant. Questionnaires were completed at a median time of 44 weeks post ventricular assist device. The 5 QOLVAD domains had acceptable construct validity (root mean square error of approximation = 0.064, comparative and Tucker-Lewis fit indices > 0.90, weighted root mean square residual = 0.95). The total score and domain-specific scores were significantly correlated with the instruments to which they were compared. Internal consistency reliability was acceptable for all subscales (α = .79-.83) except the cognitive domain (α = .66). Unidimensional reliability for the total score was acceptable (α = .93), as was factor determinacy for multidimensional reliability (0.95). Total test-retest reliability was 0.875 (P < .001). CONCLUSION: Our analysis provided initial support for validity and reliability of the QOLVAD for total score, physical, emotional, social, and meaning/spiritual domains. The QOLVAD has potential in research and clinical settings to guide decision making and referrals; further studies are needed.

Heart failure-induced activation of phospholipase iPLA2γ generates hydroxyeicosatetraenoic acids opening the mitochondrial permeability transition pore.

Congestive heart failure typically arises from cardiac myocyte necrosis/apoptosis, associated with the pathological opening of the mitochondrial permeability transition pore (mPTP). mPTP opening decreases the mitochondrial membrane potential leading to the activation of Ca2+-independent phospholipase A2γ (iPLA2γ) and the production of downstream toxic metabolites. However, the array of enzymatic mediators and the exact chemical mechanisms responsible for modulating myocardial mPTP opening remain unclear. Herein, we demonstrate that human heart failure activates specific myocardial mitochondrial phospholipases that increase Ca2+-dependent production of toxic hydroxyeicosatetraenoic acids (HETEs) and attenuate the activity of phospholipases that promote the synthesis of protective epoxyeicosatrienoic acids (EETs). Mechanistically, HETEs activated the Ca2+-induced opening of the mPTP in failing human myocardium, and the highly selective pharmacological blockade of either iPLA2γ or lipoxygenases attenuated mPTP opening in failing hearts. In contrast, pharmacological inhibition of cytochrome P450 epoxygenases opened the myocardial mPTP in human heart mitochondria. Remarkably, the major mitochondrial phospholipase responsible for Ca2+-activated release of arachidonic acid (AA) in mitochondria from non-failing hearts was calcium-dependent phospholipase A2ζ (cPLA2ζ) identified by sequential column chromatographies and activity-based protein profiling. In contrast, iPLA2γ predominated in failing human myocardium. Stable isotope kinetics revealed that in non-failing human hearts, cPLA2ζ metabolically channels arachidonic acid into EETs, whereas in failing hearts, increased iPLA2γ activity channels AA into toxic HETEs. These results mechanistically identify the sequelae of pathological remodeling of human mitochondrial phospholipases in failing myocardium. This remodeling metabolically channels AA into toxic HETEs promoting mPTP opening, which induces necrosis/apoptosis leading to further progression of heart failure.

Durable left ventricular assist device implantation in extremely obese heart failure patients.

Left ventricular assist devices (LVADs) have improved clinical outcomes and quality of life for those with end-stage heart failure. However, the costs and risks associated with these devices necessitate appropriate patient selection. LVAD candidates are becoming increasingly more obese and there are conflicting reports regarding obesity's effect on outcomes. Hence, we sought to evaluate the impact of extreme obesity on clinical outcomes after LVAD placement. Consecutive LVAD implantation patients at our center from June 2008 to May 2016 were studied retrospectively. We compared patients with a body mass index (BMI) ≥40 kg/m2 (extremely obese) to those with BMI < 40 kg/m2 with respect to patient characteristics and surgical outcomes, including survival. 252 patients were included in this analysis, 30 (11.9%) of whom met the definition of extreme obesity. We found that patients with extreme obesity were significantly younger (47[33, 57] vs. 60[52, 67] years, P < 0.001) with fewer prior sternotomies (16.7% vs. 36.0%, P = 0.04). They had higher rates of pump thrombosis (30% vs. 9.0%, P = 0.003) and stage 2/3 acute kidney injury (46.7% vs. 27.0%, P = 0.003), but there were no differences in 30-day or 1-year survival, even after adjusting for age and clinical factors. Extreme obesity does not appear to place LVAD implantation patients at a higher risk for mortality compared to those who are not extremely obese; however, extreme obesity was associated with an increased risk of pump thrombosis, suggesting that these patients may require additional care to reduce the need for urgent device exchange.

Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. METHODS: In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. CONCLUSIONS: Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493.).

Utilization of high donor sequence number grafts in cardiac transplantation.

Donor sequence number (DSN) represents the number of candidates to whom a graft was offered and declined prior to acceptance for transplantation. We sought to investigate the outcomes of patients receiving high DSN grafts. Consecutive isolated adult cardiac transplantations performed at a single-center were reviewed. Recipients were grouped into standard (≤75th percentile) DSN and high (>75th percentile) DSN. A previously validated donor risk index was used to quantify the risk associated with donor grafts, and recipient outcomes were assessed. Overall, 254 patients were included: 194 standard DSN (range 1-79) and 60 high DSN (range 82-1723). High DSN grafts were harvested at greater distance (P < .001) with increased ischemia time (P < .001), resulting in a modest increase in donor risk index (1 point median difference, P = .014). High DSN recipients were less frequently listed as UNOS status 1A (P < .001). Despite a nonsignificant trend toward increased in-hospital/30-day mortality in high DSN recipients, there were no differences in primary graft dysfunction or 1-year survival (high DSN 89% vs standard DSN 88%, P = .82). After adjustment for risk factors, high DSN was not associated with increased 1-year mortality (hazard ratio 1.18, 95%-CI 0.54-2.58, P = .68).

Rational Heart Transplant From a Hepatitis C Donor: New Antiviral Weapons Conquer the Trojan Horse.

BACKGROUND: Donors with hepatitis C (HCV) viremia are rarely used for orthotopic heart transplantation (HT) owing to post-transplantation risks. New highly effective HCV antivirals may alter the landscape. METHODS: An adult patient unsuitable for bridging mechanical support therapy accepted a heart transplant offer from a donor with HCV viremia. On daily logarithmic rise in HCV viral load and adequate titers to ensure successful genotyping, once daily sofosbuvir (400 mg)-velpatasvir (100 mg) (Epclusa; Gilead) was initiated empirically pending HCV genotype (genotype 3a confirmed after initiation of therapy). RESULTS: We report the kinetics of acute hepatitis C viremia and therapeutic response to treatment with a new pangenotypic antiviral agent after donor-derived acute HCV infection transmitted incidentally with successful cardiac transplantation to an HCV-negative recipient. Prompt resolution of viremia was noted by the 1st week of a 12 week course of antiviral therapy. Sustained virologic remission continued beyond 12 weeks after completion of HCV therapy (SVR-12). CONCLUSIONS: The availability of effective pangenotypic therapy for HCV may expand donor availability. The feasibility of early versus late treatment of HCV remains to be determined through formalized protocols. We hypothesize pharmacoeconomics to be the greatest limitation to widespread availability of this promising tool.

Arrhythmogenic Right Ventricular Dysplasia: An Under-recognized Form of Inherited Cardiomyopathy.

We report a case of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVD) in order to evaluate the course of an under-recognized form of cardiomyopathy with a vast array of clinical manifestations. The patient is a 49-year-old white woman transferred from an outside hospital due to dyspnea and persistent hypoxia. She had a pertinent family history that included a sister who died suddenly in her 30s from unexplained heart failure. Initial work-up for hypoxia was unrevealing. Transthoracic echocardiography revealed isolated right ventricular dysfunction with dilation and multiple trabeculations. Further investigation, including cardiac computed tomography and magnetic resonance imaging, revealed fatty infiltration into the right ventricular wall suggestive of ARVD.

Sex affects myocardial blood flow and fatty acid substrate metabolism in humans with nonischemic heart failure.

BACKGROUND: In animal models of heart failure (HF), myocardial metabolism shifts from high-energy fatty acid (FA) metabolism toward glucose. However, FA (vs glucose) metabolism generates more ATP/mole; thus, FA metabolism may be especially advantageous in HF. Sex modulates myocardial blood flow (MBF) and substrate metabolism in normal humans. Whether sex affects MBF and metabolism in patients with HF is unknown. METHODS AND RESULTS: We studied 19 well-matched men and women with nonischemic HF (EF ≤ 35%). MBF and myocardial substrate metabolism were quantified using positron emission tomography. Women had higher MBF (mL/g/minute), FA uptake (mL/g/minute), and FA utilization (nmol/g/minute) (P < 0.005, P < 0.005, P < 0.05, respectively) and trended toward having higher FA oxidation than men (P = 0.09). These findings were independent of age, obesity, and insulin resistance. There were no sex-related differences in fasting myocardial glucose uptake or metabolism. Higher MBF was related to improved event-free survival (HR 0.31, P = 0.02). CONCLUSIONS: In nonischemic HF, women have higher MBF and FA uptake and metabolism than men, irrespective of age, obesity, or insulin resistance. Moreover, higher MBF portends a better prognosis. These sex-related differences should be taken into account in the development and targeting of novel agents aimed at modulating MBF and metabolism in HF.

HeartMate II Left Ventricular Assist Device Pump Exchange: A Single-Institution Experience.

Background Left ventricular assist devices (LVADs) have revolutionized the treatment of patients with end-stage heart failure. These devices are replaced when pump complications arise if heart transplant is not possible. We present our experience with HeartMate II (HMII (Thoratec, Plesanton, California, United States)) LVAD pump exchange. Materials and Methods We retrospectively reviewed all cases that required pump exchange due to LVAD complication from November 2011 until June 2016 at a single high-volume institution. The indications, demographics, and outcome were extracted and analyzed. Results Of 250 total patients with implanted HMII LVADs, 16 (6%) required pump exchange during the study period. The initial indications for LVAD placement in these patients were bridge to transplantation (n = 6 [37.5%]) or destination therapy (n = 10 [62.5%]). Fifteen patients (93.8%) required pump exchange due to pump thrombosis and 1 (6.2%) due to refractory driveline infection. Nine patients (56.2%) underwent repeat median sternotomy while a left subcostal approach was used in the remaining seven patients. Fifteen patients (93.7%) survived until hospital discharge. During the follow-up period (median, 155 days), 11 patients remained alive and 4 of these underwent successful cardiac transplantation. Conclusion HMII LVAD pump exchange can be safely performed for driveline infection or pump thrombosis when heart transplantation is not an option.

Women With Cardiogenic Shock Derive Greater Benefit From Early Mechanical Circulatory Support: An Update From the cVAD Registry.

OBJECTIVES: The aim of this analysis was to assess survival differences between men and women supported with Impella 2.5 (Abiomed Inc., Danvers) in the setting of acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). BACKGROUND: Data on sex differences in outcomes of CS with mechanical circulatory support are sparse. METHODS: Patients enrolled in the cVAD Registry who underwent percutaneous coronary intervention (PCI) and Impella 2.5 support for CS complicating an AMI were included. Differences between men and women were examined. RESULTS: In total, 180 patients were analyzed. Women (n = 49, 27.2%) were older (71.0 ± 12.8 years vs 63.8 ± 13.0, P = 0.001), smaller (BSA 1.82 ± 0.22 vs 2.04 ± 0.24 m(2) , P < 0.001), and had a higher STS mortality risk score than men (27.9 ± 17.0 vs. 20.8 ± 16.8 P = 0.01). There was no difference in survival to discharge (P = 0.3). Patients receiving the Impella 2.5 pre-PCI had significantly lower inpatient mortality than those who received support post-PCI (P = 0.003). However, the magnitude of the survival benefit was significantly greater in women who received the Impella pre-PCI as compared to men. Overall, 68.8% of women survived with pre-PCI Impella 2.5 versus 24.2% post-PCI (P = 0.005) whereas 54.2% of men survived with pre-PCI Impella 2.5 versus 40.3% post-PCI (P = 0.1, p-interaction = 0.07). No differences in timing to intervention were found between men and women. CONCLUSIONS: Early initiation of hemodynamic support prior to PCI with Impella 2.5, in the setting of AMI complicated by CS, was associated with a greater survival benefit to hospital discharge in women compared to men, despite a higher predicted risk of mortality and a greater revascularization failure rate for women. (J Interven Cardiol 2016;29:248-256).

Intra-Aortic Balloon Counterpulsation in Patients With Chronic Heart Failure and Cardiogenic Shock: Clinical Response and Predictors of Stabilization.

OBJECTIVE: The aim of this work was to characterize the clinical response and identify predictors of clinical stabilization after intra-aortic balloon counterpulsation (IABP) support in patients with chronic systolic heart failure in cardiogenic shock before implantation of a left ventricular assist device (LVAD). BACKGROUND: Limited data exist regarding the clinical response to IABP in patients with chronic heart failure in cardiogenic shock. METHODS: We identified 54 patients supported with IABP before LVAD implantation. Criteria for clinical decompensation after IABP insertion and before LVAD included the need for more advanced temporary support, initiation of mechanical ventilation or dialysis, increase in vasopressors/inotropes, refractory ventricular arrhythmias, or worsening acidosis. The absence of these indicated stabilization. RESULTS: Clinical decompensation after IABP occurred in 23 patients (43%). Both patients who decompensated and those who stabilized had similar hemodynamic improvements after IABP support, but patients who decompensated required more vasopressors/inotropes. Clinical decompensation after IABP was associated with worse outcomes after LVAD implantation, including a 3-fold longer intensive care unit stay and 5-fold longer time on mechanical ventilation (P < .01 for both). Although baseline characteristics were similar between groups, right and left ventricular cardiac power indexes (cardiac power index = cardiac index × mean arterial pressure/451) identified patients who were likely to stabilize (area under the receiver operating characteristic curve = 0.82). CONCLUSIONS: Among patients with chronic systolic heart failure who develop cardiogenic shock, more than one-half of patients stabilized with IABP support as a bridge to LVAD. Baseline measures of right and left ventricular cardiac power, reflecting work performed for a given flow and pressure, may allow clinicians to identify patients with sufficient contractile reserve who will be likely to stabilize with an IABP versus those who may need more aggressive ventricular support.

Characteristics of the electrocardiogram in patients with continuous-flow left ventricular assist devices.

BACKGROUND: Electrocardiograms (ECGs) are routinely obtained in patients with advanced congestive heart failure (CHF) before and after surgical implantation with a left-ventricular assist device (LVAD). As the number of patients with CHF is increasing, it is necessary to characterize the changes present in the ECG of patients with LVADs. METHODS: ECGs of 43 patients pre- and postimplantation of a HeartMate II LVAD were compared to characterize the presence of an LVAD using the following six criteria (LVADS2 ): low limb-lead voltage, ventricular pacing, artifact (electrical), duration of the QRS > 120 milliseconds, ST-elevation in the lateral leads, and splintering of the QRS complex. Additionally, 50 ECGs of non-LVAD patients coded as "lateral myocardial infarction (MI)" and 50 ECGs coded as "ventricular pacing" were chosen at random and scored. Odds ratios were calculated using Fisher's exact test. Logistic regression models were built to predict the presence of an LVAD in all patients. RESULTS: Univariate analysis of the pre- and post-LVAD ECGs confirmed that all criteria except the "Duration of QRS > 120 milliseconds" characterized the ECG of a patient with an LVAD. Electrical artifact and low limb-lead voltage yielded the greatest association with an LVAD-ECG. CONCLUSIONS: The ECG of a patient with end-stage CHF significantly changes with LVAD implantation. The LVADS2 criteria provide a framework towards characterizing and establishing a new baseline of the ECG in a patient with a continuous-flow LVAD.

Rituximab is associated with improved survival in cardiac allograft patients with antibody-mediated rejection: a single center review.

Antibody-mediated rejection (AMR) after cardiac transplantation is associated with significant mortality, and the optimal treatment of this condition is poorly defined. Rituximab has been used successfully for the treatment for antibody-mediated diseases; however, its role in AMR is unclear. We review our experience with rituximab in patients with cardiac allograft AMR. We conducted a retrospective analysis of cardiac transplant patients with a diagnosis of AMR from 2001 to 2011. Inclusion criteria were clinical suspicion of rejection with the presence of C4d complement staining on endomyocardial biopsy and the absence of cellular rejection of grade 2R or greater. Patients were divided into Rituximab and NoRituximab groups. The primary endpoint was all-cause mortality. Secondary endpoints were infection, change in ejection fraction (EF), and rehospitalization. Thirty-three patients met inclusion criteria, of whom 13 received rituximab and 20 did not. Baseline characteristics were similar between groups. Kaplan-Meier curves for a three-yr follow-up period demonstrate improved survival in the Rituximab group (p = 0.0089). There were no differences in secondary endpoints. We found that rituximab therapy was associated with improved survival in cardiac allograft AMR. Further prospective, randomized studies in larger patient populations are needed to confirm this finding and to define ideal timing for rituximab administration.

Noninvasive mapping of ventricular activation in patients with transplanted hearts.

This is the first reported study of ventricular activation patterns after cardiac transplantation, using electrocardiographic imaging (ECGI), a noninvasive method for electrophysiologic mapping. This study of ten patients reveals that transplanted hearts have unique ventricular activation patterns in sinus rhythm, activating early in the epicardial aspect of the anterior or inferior septum, with intact right and left bundle branch conduction. They have late activation with slowing of conduction near the right ventricular (RV) basal free wall, causing a mild QRS prolongation and an rSr' pattern in lead V1 of the ECG. PVCs arise from both endocardial and epicardial locations in both ventricles.