Effectiveness of combined plasma cell therapy and costimulation blockade based desensitization regimen in heart transplant candidates.

BACKGROUND: Desensitization is one of the strategies to reduce antibodies and facilitate heart transplantation in highly sensitized patients. We describe our center's desensitization experience with combination of plasma cell (PC) depletion therapy (with proteasome inhibitor or daratumumab) and costimulation blockade (with belatacept). METHODS: We reviewed five highly sensitized patients who underwent desensitization therapy with plasma cell depletion and costimulation blockade. We evaluated the response to therapy by measuring the changes in cPRA, average MFI, and number of positive beads > 5000MFI. RESULTS: Five patients, mean age of 56 (37-66) years with average cPRA of 98% at 5000 MFI underwent desensitization therapy. After desensitization, mean cPRA decreased from 98% to 70% (p = .09), average number of beads > 5000 MFI decreased from 59 to 37 (p = .15), and average MFI of beads > 5000 MFI decreased from 16713 to 13074 (p = .26). CONCLUSION: Combined PC depletion and CoB could be a reasonable strategy for sustained reduction in antibodies in highly sensitized patients being listed for heart transplantation.

Intravenous immunoglobulin in heart transplant recipients with mild to moderate hypogammaglobulinemia and infection.

BACKGROUND: Hypogammaglobulinemia (HGG) is a complication of solid organ transplantation leading to increased risk of infections. Intravenous immunoglobulin G (IVIG) replacement in patients with HGG may be able to reduce risk and morbidity associated with infection; however, there is scarce data about IVIG in mild to moderate HGG (IgG 400-700 mg/dl) and heart transplant recipients. METHODS: A single center, retrospective study was performed in heart transplant recipients with mild (IgG 500-700 mg/dl) to moderate (IgG 400-499 mg/dl) HGG in the presence of an infection. RESULTS: Forty-two patients were included in this study; 19 patients (45.2%) received IVIG and 23 (54.8%) patients did not. Patients in the IVIG group received on average one dose of IVIG at 0.5 g/kg. No differences in incidence of new infection at 3 months (26.3% vs. 17.4%; P = .71) and 6 months (42.1% vs. 34.8%; P = .63) were observed between the IVIG and non-IVIG groups. Infections based on mild or moderate HGG also had no differences at 3 and 6 months. CONCLUSION: Our findings suggest that a single infusion of IVIG in mild to moderate HGG may have little to no benefit in reducing incidence of new infections. Larger prospective studies are needed to confirm these findings.

Utilization of Left Ventricular Assist Devices in Vulnerable Adults Across Medicaid Expansion.

BACKGROUND: Continuous-flow left ventricular assist device (LVAD) implantation is a payor sensitive procedure influenced by preoperative comorbidities and social factors. Whether expansion in insurance coverage will further influence device utilization is unknown. This study sought to assess the effects of Medicaid expansion on vulnerable populations (namely racial-ethnic minorities and those with low-income status) undergoing continuous-flow LVAD implantation after the enactment of the 2014 Affordable Care Act (ACA). METHODS: Data from the 2012 to Q3 2015 State Inpatient Database were used to examine a cohort of 624 nonelderly adults (aged 18-64 y) who were given a continuous-flow LVAD in three expansion states (Kentucky, New Jersey, and Maryland) and two nonexpansion states (North Carolina and Florida). The cohort excluded patients who had a heart transplant, heart-lung transplant, or noncontinuous-flow LVAD. Poisson Interrupted Time Series was used with three-way interactions and change of slope and intercept parameters at 2014 to determine the impact of the ACA expansion on utilization of continuous-flow LVAD by race and insurance strata. RESULTS: Poisson Interrupted Time Series models show that within expansion states, the population of Medicaid and uninsured patients saw an increase in the utilization of LVAD's immediately after ACA expansion, from 2.8 in Q4 2013 to 9.83 Q1 2014 (incidence rate ratio [IRR] 5.26, P = 0.02). Utilization eventually declined to pre-ACA levels, however, ending with 3.04 LVADs in Q3 2015 (IRR 0.84, 95% confidence interval 0.58-1.20). Models testing for racial effect showed no statistically preferential or disparate effects (immediate effect IRR 1.608, P = 0.506; marginal effect IRR 0.897, P = 0.512). CONCLUSIONS: These findings show that despite expanded insurance coverage, the utilization of continuous-flow LVADs was not increased in nonelderly racial and ethnic minorities following the ACA Medicaid expansion. Although these findings are preliminary and require further long-term evaluation, they suggest that insurance coverage alone does not play a significant role in increased utilization of continuous-flow LVAD. These findings point toward the importance of further exploring social, medical, and hospital drivers of these disparities.

The association between novel clinical factors and gastrointestinal bleeding among patients supported with continuous-flow left ventricular assist device therapy.

BACKGROUND: This study explores novel preimplantation risk factors associated with gastrointestinal bleeding (GIB) after continuous-flow left ventricular assist device (CF-LVAD) implantation. CF-LVAD therapy implantation for patients with advanced heart failure is associated with a 20% to 40% incidence of GIB. METHODS: This study includes patients receiving CF-LVAD at a quaternary medical center from 2006 to 2014 (n = 254). The primary endpoint was GIB within 12 months after implantation; the secondary outcome was 3-year all-cause mortality. The Student t test or the χ2 test compared continuous or categorical variables. Competing risks analysis calculated the cumulative incidence of GIB postimplantation. Cox proportional hazards model was used for univariate/multivariate models predicting GIB. RESULTS: Sixty-four patients had GIB, with incidence rates at 1, 3, and 12 months of 11.8%, 19.3%, and 25.2%, respectively. Endoscopy revealed no identified source of bleeding in 41%; 33% of lesions were localized in the upper gastrointestinal tract, with the bulk (39%) categorized as vascular. Patients with prior gastrointestinal abnormalities (n = 98) had a greater risk of GIB post-CF-LVAD (HR 1.85 [1.11-3.09]; P = 0.02) than those with normal gastrointestinal evaluation results (n = 45) and those without preimplantation gastrointestinal evaluation (n = 111). Baseline blood urea nitrogen, chronic obstructive pulmonary disease, and prior percutaneous coronary intervention were statistically associated with post-CF-LVAD GIB. The presence of GIB within 12 months of CF-LVAD implantation was associated with an increased risk of 3-year all-cause mortality (HR 2.57 [1.57-4.15]; P < 0.01). CONCLUSIONS: First-year GIB is associated with increased mortality post-CF-LVAD. We advocate a closer examination of several GIB risk factors when evaluating CF-LVAD candidates.

Relationship of cardiac troponin to systolic global longitudinal strain in hypertrophic cardiomyopathy.

BACKGROUND: A high proportion of stable hypertrophic cardiomyopathy (HCM) patients have elevated serum cardiac troponin I (cTnI), but its clinical and echocardiographic determinants are unknown. Our objective was to determine the prevalence and clinical predictors of positive troponin (cTnI+) in a well-defined population of HCM patients using a highly sensitive assay. METHODS: We retrospectively interrogated medical records of 167 stable HCM patients from 1/2011 to 3/2014. cTnI >0.04 ng/mL was considered positive. RESULTS: Thirty-four percent were troponin-positive (median cTnI was 0.1 [0.07, 0.2] ng/dL). cTnI as a continuous variable correlated positively with maximal left ventricular wall thickness (LVT), maximal interventricular septal thickness, and global longitudinal strain (GLS) (P<.001). Unadjusted OR (95% CI) for positive troponin was 0.5 (0.3-0.9, P=.05) for obstructive HCM, 3.2 (1.7-5.9, P<.0001) for increased LVT, 0.3 (0.2-0.6, P<.0001) for -5% increase in GLS, 0.2 (0.04-0.9, P=.04) for moderate-to-severe mitral regurgitation, and 1.9 (0.9-3.9, P=.06) for implantable cardioverter defibrillator history. After adjusting for these variables, only maximum LVT (OR 2.5 [95% CI: 1.1-5.7, P=.02]) and GLS (OR 0.3 [95% CI: 0.2-0.6, P=.001]) were independent predictors. The percentage of patients with a positive cTnI increased from 19% to 24% and 57% across tertiles of LVT (P=.003) and decreased from 54% to 33% and 14% across tertiles of GLS (P<.0001). CONCLUSION: In this cohort of HCM patients, the association of reduced GLS and positive troponin was independent of LVT. Further studies are warranted to evaluate whether their combination adds prognostic value in identifying high-risk patients to define effective and early intervention strategies.

The association between ischemic and jeopardized myocardia and all-cause mortality in patients with peripheral artery disease.

Peripheral artery disease (PAD) is associated with increased mortality and concomitant coronary artery disease (CAD). However, it is unclear whether uncovering the presence of functional coronary ischemia by single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) would further help stratifying that excess risk. From January 2000 to 2009, 4294 individuals underwent cardiac stress testing within 180 days of ankle-brachial index (ABI) measurements. Of these, 645 had PAD and SPECT MPI stress testing. Abnormal ABI was defined as ⩽ 0.9 or prior lower extremity arterial revascularization. Myocardial ischemic burden and total jeopardized myocardium were represented by the summed difference score (SDS) and summed stress score (SSS), respectively. Univariate and multivariable Cox proportional hazard analyses were used to study the impact of SDS and SSS on all-cause mortality. Additionally, using a hierarchical approach, we examined the step-wise addition of post-stress test coronary and lower extremity arterial revascularizations as time-varying covariates on outcomes. We found no significant difference in all-cause mortality between patients with ischemic myocardium (SDS > 0) and those without (SDS = 0) (adjusted HR: 0.94, 95% CI: 0.53-1.69; p = 0.84). Similarly, the presence of jeopardized myocardium (SSS > 0) did not have a significant impact on mortality (adjusted HR: 1.16, 95% CI: 0.67-2.00; p = 0.59). Moreover, adjustment for post-testing coronary and lower extremity arterial revascularizations did not affect our results. In conclusion, ischemic and jeopardized myocardia are not predictors of all-cause mortality in PAD; thus, SPECT MPI does not appear to be a useful risk stratification tool in these patients.

Transient Apical Thickening Following Apical Ballooning Syndrome: A Case Series.

The authors describe transient apical thickening mimicking apical hypertrophic cardiomyopathy following apical ballooning syndrome. These findings are observed on multimodality cardiac imaging and appear to constitute a novel entity. Possible pathophysiologic mechanisms are explored.

Procedural Insights and Clinical Outcomes of a Novel Superior Vena Cava Occlusion Device for Acute Heart Failure: A Single-Center Experience.

The preCARDIA system is a device combining a balloon-mounted catheter and an extracorporeal system designed for intermittent occlusion of the superior vena cava. Studies have established safety and efficacy in acute decompensated heart failure. We present a single-center experience detailing 90 days outcomes and procedural insights. A 24 hours therapy session demonstrated reduced pulmonary wedge pressures and increased urine output, with cardiac output remaining unchanged. There was one readmission and no heart failure-related readmissions at 90 days. The preCARDIA device appears to be a safe mechanical diuretic strategy to manage patients with acute decompensated heart failure beyond current therapeutic strategies.

Mechanical Preload Reduction: Harnessing a Cornerstone of Heart Failure Management to Improve Clinical Outcomes.

Decongestion is a cornerstone therapeutic goal for those presenting with decompensated heart failure. Current approaches to clinical decongestion include reducing cardiac preload, which is typically limited to diuretics and hemofiltration. Several new technologies designed to mechanically reduce cardiac preload are in development. In this review, we discuss the pathophysiology of decompensated heart failure; the central role of targeting cardiac preload; emerging mechanical preload reduction technologies; and potential application of these devices.

Bloodstream infections in prolonged use of axillary-placed, intra-aortic balloon-pump support: A single-center study.

Infections from prolonged use of axillary intra-aortic balloon pumps (IABPs) have not been well studied. Bloodstream infection (BSI) occurred in 13% of our patients; however, no difference in outcome was noted between those with BSI and those without. Further studies regarding protocol developments that minimize BSI risk are needed.

Outflow cannula alignment in continuous flow left ventricular devices is associated with stroke.

We sought to evaluate whether differences in left ventricular assist device (LVAD) canula alignment are associated with stroke. There is a paucity of clinical data on contribution of LVAD canulae alignment to strokes. We conducted a retrospective analysis of patients who underwent LVAD implantation at Houston Methodist hospital from 2011 to 2016 and included those who had undergone cardiac computed tomography (CT) with contrast. LVAD graft alignment using X-ray, echocardiography, and cardiac CT was evaluated. The primary outcome was stroke within 1 year of LVAD implantation. Of the 101 patients that underwent LVAD Implantation and cardiac CT scan during the study period, 78 met inclusion criteria. The primary outcome occurred in 12 (15.4%) patients with a median time to stroke of 77 days (interquartile range: 42-132 days). Of these, 10 patients had an ischemic and two had hemorrhagic strokes. The predominant device type was Heart Mate II (94.8%). Patients with LVAD outflow cannula to aortic angle lesser than 37.5° and those with outflow graft diameter of anastomosis less than 1.5 cm (assessed by cardiac CT) had significantly higher stroke risk (p < 0.001 and p = 0.01 respectively). In HMII patients, a lower LVAD speed at the time of CT scan was associated with stroke. Further studies are needed to identify optimal outflow graft configuration to mitigate stroke risk.

Intermittent Occlusion of the Superior Vena Cava to Improve Hemodynamics in Patients With Acutely Decompensated Heart Failure: The VENUS-HF Early Feasibility Study.

BACKGROUND: Reducing congestion remains a primary target of therapy for acutely decompensated heart failure. The VENUS-HF EFS (VENUS-Heart Failure Early Feasibility Study) is the first clinical trial testing intermittent occlusion of the superior vena cava with the preCARDIA system, a catheter mounted balloon and pump console, to improve decongestion in acutely decompensated heart failure. METHODS: In a multicenter, prospective, single-arm exploratory safety and feasibility trial, 30 patients with acutely decompensated heart failure were assigned to preCARDIA therapy for 12 or 24 hours. The primary safety outcome was a composite of major adverse cardiovascular and cerebrovascular events through 30 days. Secondary end points included technical success defined as successful preCARDIA placement, treatment, and removal and reduction in right atrial and pulmonary capillary wedge pressure. Other efficacy measures included urine output and patient-reported symptoms. RESULTS: Thirty patients were enrolled and assigned to receive the preCARDIA system. Freedom from device- or procedure-related major adverse events was observed in 100% (n=30/30) of patients. The system was successfully placed, activated and removed after 12 (n=6) or 24 hours (n=23) in 97% (n=29/30) of patients. Compared with baseline values, right atrial pressure decreased by 34% (17±4 versus 11±5 mm Hg, P<0.001) and pulmonary capillary wedge pressure decreased by 27% (31±8 versus 22±9 mm Hg, P<0.001). Compared with pretreatment values, urine output and net fluid balance increased by 130% and 156%, respectively, with up to 24 hours of treatment (P<0.01). CONCLUSIONS: We report the first-in-human experience of intermittent superior vena cava occlusion using the preCARDIA system to reduce congestion in acutely decompensated heart failure. PreCARDIA treatment for up to 24 hours was well tolerated without device- or procedure-related serious or major adverse events and associated with reduced filling pressures and increased urine output. These results support future studies characterizing the clinical utility of the preCARDIA system. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03836079.

Misdiagnosis in the COVID-19 Era: When Zebras Are Everywhere, Don't Forget the Horses.

We describe a patient who presented with respiratory failure, chest pain, and fever. In the COVID-19 pandemic era, the focus was diverted to the coronavirus infection, and ST-segment elevation myocardial infarction was missed. Although we need to be vigilant in the diagnosis of COVID-19, we should not forget about the common disorders. (Level of Difficulty: Beginner.).

Transcatheter Aortic Valve Replacement of a Bicuspid Aortic Valve in a Heart Transplant Recipient.

Patients with heart transplants who present with severe aortic stenosis may be deemed high-risk surgical candidates due to immunosuppression and multiple comorbid conditions. Appropriately selected patients may be successfully treated with transcatheter aortic valve replacement. (Level of Difficulty: Advanced.).

Right Ventricular Failure Post-Implantation of Left Ventricular Assist Device: Prevalence, Pathophysiology, and Predictors.

Despite advances in left ventricular assist device (LVAD) technology, right ventricular failure (RVF) continues to be a complication after implantation. Most patients undergoing LVAD implantation have underlying right ventricular (RV) dysfunction (either as a result of prolonged LV failure or systemic disorders) that becomes decompensated post-implantation. Additional insults include intra-operative factors or a sudden increase in preload in the setting of increased cardiac output. The current literature estimates post-LVAD RVF from 3.9% to 53% using a diverse set of definitions. A few of the risk factors that have been identified include markers of cardiogenic shock (e.g., dependence on inotropes and Interagency Registry for Mechanically Assisted Circulatory Support profiles) as well as evidence of cardiorenal or cardiohepatic syndromes. Several studies have devised multivariable risk scores; however, their performance has been limited. A new functional assessment of RVF and a novel hepatic marker that describe cholestatic properties of congestive hepatopathy may provide additional predictive value. Furthermore, future studies can help better understand the relationship between pulmonary hypertension and post-LVAD RVF. To achieve our ultimate goal-to prevent and effectively manage RVF post-LVAD-we must start with a better understanding of the risk factors and pathophysiology. Future research on the different etiologies of RVF-ranging from acute post-surgical complication to late-onset RV cardiomyopathy-will help standardize definitions and tailor therapies appropriately.

Benefits of Neurohormonal Therapy in Patients With Continuous-Flow Left Ventricular Assist Devices.

Left ventricular assist devices (LVADs) have dramatically improved short-term outcomes among patients with advanced heart failure. While neurohormonal blockade (NHB) is the cornerstone of treatment for patients with heart failure with reduced ejection fraction, its effect after LVAD placement has not been established. We reviewed medical records of 307 patients who underwent primary LVAD implantation from January 2006 to September 2015 at two institutions in the United States. Patients were followed for at least 2 years post-LVAD implantation or until explantation, heart transplantation, or death. Cox regression analysis stratifying on center was used to assess associations with mortality. Neurohormonal blockade use was treated as a time-dependent predictor. Stepwise selection indicated treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) (hazard ratio [HR] = 0.53 [0.30-0.95], p = 0.03), age at the time of implantation (HR = 1.28 [1.05-1.56] per decade, p = 0.02), length of stay postimplantation (HR = 1.16 [1.11-1.21] per week, p < 0.01) and INTERMACS profile of 1 or 2 (HR = 1.86 [1.17-2.97], p < 0.01) were independent predictors of mortality. In this large, retrospective study, treatment with ACEIs or ARBs was an independent factor associated with decreased mortality post-LVAD placement.

Ventricular Septal Dissection Complicating Inferior Wall Myocardial Infarction.

Postmyocardial infarction ventricular septal defect is an increasingly rare mechanical complication of acute myocardial infarction. We present a case of acute myocardial infarction from right coronary artery occlusion that developed hypotension and systolic murmur 12 hours after successful percutaneous coronary intervention. Although preoperative imaging suggested a large ventricular septal defect and a pseudoaneurysm, intraoperative findings concluded a serpiginous dissection of the ventricular septum. The imaging technicalities are discussed.

Hypertrophic cardiomyopathy with aortic dilation: a novel observation.

AIMS: Our goal was to identify the prevalence of aortic dilation in patients with hypertrophic cardiomyopathy (HCM), the most prevalent (0.2%) heritable, genetic cardiovascular disease. Aortic dilation also represents a spectrum of familial inheritance. However, data regarding the prevalence of aortic dilation in HCM patients is lacking. METHODS AND RESULTS: This is an observational retrospective study of all patients referred to our HCM centre. Aortic dilation was defined based on recent American Society of Echocardiography and European Association of Cardiovascular Imaging published guidelines. Of the 201 HCM patients seen between Jan. 1, 2011 and March 31, 2014, 18 (9.0%) met the definition of aortic dilation. Mean age was 56.3 ± 9.3 years, 77.8% were male, mean ascending aorta diameter was 4.0 ± 0.4 cm in males and 3.8 ± 0.2 cm in females, mean sinuses of Valsalva diameter was 4.2 ± 0.2 cm in males and 3.8 ± 0.4 cm in females, and 13 (72.2%) had left ventricular outflow tract obstruction. HCM patients with dilated aorta were more likely males, less likely hypertensive and had larger left ventricle diameter and more aortic valve regurgitation; remaining characteristics were similar. CONCLUSION: We report a novel observation with 9.0% prevalance of dilated aorta in HCM patients. Further studies are needed to help define the genetic and pathophysiologic basis as well as the clinical implications of this association in a larger group of HCM patients.