ATTR Gene Variants in HCM.

Hypertrophic cardiomyopathy is the most common inherited cardiomyopathy, with a prevalence of 1:200 to 1:500. Cardiac amyloidosis, another cardiomyopathy caused by myocardial deposition of abnormally folded TTR protein, can be acquired or hereditary. The presence of pathogenic TTR gene variants in patients with phenotypic HCM is an underrecognized and clinically important entity.

Significant vascular complications in percutaneous axillary intra-aortic balloon pump.

OBJECTIVE: Axillary Intra-aortic balloon pump (IABP) has been increasingly utilized for hemodynamic support in heart failure patients. Vascular complications associated with axillary IABP such as dissection or rupture are relatively rare but not negligible that could negatively affect clinical outcomes. We summarized our experiences. METHODS: This is a retrospective study reviewing of all patients receiving an axillary IABP between June 2016 and November 2020. A total of 199 patients underwent percutaneous axillary IABP placement. 6 patients (6/199, 3.0%) were complicated with arterial/aortic dissection or rupture during the procedures or the course of treatment. We described their clinical presentations and outcomes. RESULTS: Vascular complications included acute type A aortic dissection in 2 patients, descending aortic rupture in 1 patient, abdominal aortic rupture along with type B aortic dissection in 1 patient, and the localized left subclavian artery dissection in 2 patient. 2 type A aortic dissection cases were surgically treated: 1 with emergent left ventricle assist device and ascending aorta replacement, the other with emergent left ventricle assist device. Emergent endovascular treatment was successfully performed in 2 aortic rupture cases. The left subclavian artery dissection cases were managed medically. The postoperative/treatment course was uneventful in all patients. CONCLUSION: Percutaneous axillary IABP therapy can cause significant vascular complications. Early diagnosis and prompt treatment would be the key to improve the clinical outcomesv.

Proximal ascending aorta size is associated with the incidence of de novo aortic insufficiency with left ventricular assist device.

We sought to assess the impact of the aortic root geometry on developing de novo aortic insufficiency (AI) in patients undergoing left ventricular assist device (LVAD). In total, 114 patients underwent LVAD implantation between February 2016 and January 2020 were included in this study (HeartMate3 N = 68, HeartWare N = 46). Significant aortic insufficiency was defined as mild-to-moderate or greater in echocardiography. The cohort was divided into two groups; those who developed significant AI (Group AI: n = 13) and did not (Group non-AI: n = 101). The primary outcomes of interest included late survival and predictors for significant AI. The patients in Group AI were older than Group non-AI (62.6 ± 11.9 vs 51.3 ± 14.0 years, p < 0.01). The diameter of proximal ascending aorta in Group AI was larger than Group non-AI (31.0 ± 5.0 vs 27.4 ± 4.3 mm, p < 0.01). Aortic valve remained closed in 53.8% in Group AI and 36.6% in Group non-AI (p = 0.24). The late survival was not significantly different between the groups (67.1% vs 76.0% at 3 years, log rank = 0.97). The Cox hazard model showed that larger proximal ascending aortic diameter/BSA (HR 1.55, CI 1.19-2.04, p < 0.01) and not-opening aortic valve (HR 4.73, CI 1.43-16.9, p = 0.01) were independent risk factors for significant AI. The cutoff value of proximal ascending aortic diameter/BSA was 15.5 (area under curve: 0.770, sensitivity: 0.69, specificity: 0.79). Dilated proximal ascending aorta at the time of LVAD surgery and not-opening aortic valve during follow-up were associated with the incidence of de novo significant AI.

VE/VCO2 slope predicts RV dysfunction and mortality after left ventricular assist device: a fresh look at cardiopulmonary stress testing for prognostication.

Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in prognostication after LVAD surgery has never been studied. VE/VCO2 slope is an important component of CPET which has direct pathophysiologic links to right ventricular (RV) performance. We hypothesized that VE/VCO2 slope would prognosticate RV dysfunction after LVAD. All CPET studies from a single institution were collected between September 2009 and February 2019. Patients who ultimately underwent LVAD implantation were selectively analyzed. Peak VO2 and VE/VCO2 slope were measured for all patients. We evaluated their association with hemodynamic, echocardiographic and clinical markers of RV dysfunction as well mortality. Patients were stratified into those with a ventilatory class of III or greater. (VE/VCO2 slope of ≥ 36, n = 43) and those with a VE/VCO2 slope < 36 (n = 27). We compared the mortality between the 2 groups, as well as the hemodynamic, echocardiographic and clinical markers of RV dysfunction. 570 patients underwent CPET testing. 145 patients were ultimately referred to the advanced heart failure program and 70 patients later received LVAD implantation. Patients with VE/VCO2 slope of ≥ 36 had higher mortality (30.2% vs. 7.4%, p = 0.02) than patients with VE/VCO2 slope < 36 (n = 27). They also had a higher incidence of clinically important RVF (Acute severe 9.3% vs. 0%, Severe 32.6% vs 25.9%, p = 0.03). Patients with a VE/VCO2 slope ≥ 36 had a higher CVP than those with a lower VE/VCO2 slope (11.2 ± 6.1 vs. 6.0 ± 4.8 mmHg, p = 0.007), and were more likely to have a RA/PCWP ≥ 0.63 (65% vs. 19%, p = 0.008) and a PAPI ≤ 2 (57% vs. 13%, p = 0.008). In contrast, peak VO2 < 12 ml/kg/min was not associated with postoperative RV dysfunction or mortality. Elevated preoperative VE/VCO2 slope is a predictor of postoperative mortality, and is associated with postoperative clinical and hemodynamic markers of impaired RV performance.

Discordance between immunofluorescence and immunohistochemistry C4d staining and outcomes following heart transplantation.

BACKGROUND: Capillary deposition of C4d is an important marker of antibody-mediated rejection (AMR) following heart transplantation (HT). There are two immunopathologic assay methods for detecting C4d: frozen-tissue immunofluorescence (IF) and paraffin immunohistochemistry (IHC). The clinical significance of discrepancy between the results of IF and IHC has not been understood. METHODS AND RESULTS: We reviewed 2187 biopsies from 142 HT recipients who had biopsies with assessment of both IF and IHC staining. Among them, 103 (73%) patients had negative IF and IHC C4d staining (Negative Group) and 32 (23%) patients had positive IF but negative IHC staining (Discordant Group). At the time of positive biopsy, 6 (19%) Discordant patients had graft dysfunction, compared to 5 (5%) Negative patients (p = .022). Cumulative incidence of cellular rejection at 1 year was comparable (31% vs. 29%, p = .46); however, cumulative incidence of AMR was significantly higher in the Discordant group (21% vs. 4%, p = .004). Overall 1-year survival was comparable (90% vs. 96%, p = .24); however, freedom from heart failure (HF) was significantly lower in the Discordant group (70% vs. 96%, p < .001). CONCLUSION: The Discordant group showed higher rates of graft dysfunction, AMR and HF admission than the Negative group.

Outcomes of Ambulatory Axillary Intraaortic Balloon Pump as a Bridge to Heart Transplantation.

BACKGROUND: The axillary intraaortic balloon pump (IABP) is frequently used in selected patients for circulatory support as a bridge to heart transplantation. The purpose of this study was to investigate the safety and efficacy of axillary intraaortic balloon pump (IABP) support for heart transplant candidates. METHODS: The study investigators collected data on 133 patients who underwent axillary IABP support as a bridge to transplantation from July 2009 to April 2019. Of these patients, 94 (70.7%) underwent IABP insertion with surgical axillary grafts, and 39 (29.3%) underwent percutaneous IABP insertion. The outcomes of interest included ambulatory data, IABP-related complications, and successful heart transplantation with this type of support. RESULTS: The overall preoperative ejection fraction was 20.3% ± 8.0%. The median duration of axillary IABP support was 21days, with 131patients (98.5%) mobilizing with the device. Hemodynamic variables significantly improved after the axillary IABP support was placed. Overall, 122 patients (91.7%) were successfully bridged to heart transplantation. Six patients (4.5%) required escalation to further mechanical support. Two patients (1.5%) died while awaiting transplantation. Four patients (3.0%) experienced a stroke during axillary IABP support (3 before transplantation and1 after transplantation). Two of the 3 patients with a stroke diagnosis before transplantation recovered and eventually underwent heart transplantation. CONCLUSIONS: With axillary IABP support, most patients were able to ambulate and undergo physical rehabilitation while waiting for heart transplantation. This study demonstrates that axillary IABP results in a high success rate of bridge to transplantation and a low number of complications. Thus, an ambulatory axillary IABP provided efficient and safe support for selected patients as a bridge to heart transplantation.

HeartWare Ventricular Assist Device Cannula Position and Hemocompatibility-Related Adverse Events.

BACKGROUND: HeartWare ventricular assist device (HVAD) cannula position is associated with hemodynamics and heart failure readmissions. However, its impact on hemocompatibility-related adverse events (HRAEs) remains uncertain. METHODS: HVAD patients were followed for 1 year after index hospitalization, when cannula coronal angle was quantified from chest x-ray film. Invasive right heart catheterization and transthoracic echocardiography were performed. One-year occurrences of each HRAE were compared between those with and without a cannula coronal angle of greater than 65 degrees. RESULTS: Among 63 HVAD patients (median age 60 years, 63% male), 10 (16%) had a cannula coronal angle greater than 65 degrees. The wide-angle group had elevated intracardiac pressures and lower pulmonary artery pulsatility index (P < .05). They also had reduced right ventricular function by echocardiography. Freedom from HRAEs tended to be lower in the wide-angle group (24% vs 62%; P = .11). The rate of gastrointestinal bleeding was significantly higher in the greater than 65 degrees group (0.90 events/year vs 0.40 events/year; P = .013). The rates of stroke and pump thrombosis were statistically comparable irrespective of cannula angle (P > .05). CONCLUSIONS: HVAD cannula coronal angle was associated with reduced right ventricular function and HRAEs. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on HRAEs are warranted.

Effect of Concomitant Tricuspid Valve Surgery With Left Ventricular Assist Device Implantation.

BACKGROUND: Tricuspid regurgitation (TR) is common in advanced heart failure (HF) patients. However, the effect of concomitant tricuspid valve repair or replacement (tricuspid valve intervention [TVI]) with left ventricular assist device (LVAD) implantation is controversial. The aim of this study was to investigate the longitudinal trend of TR after LVAD implantation and the effect of TVI on the TR trend and clinical outcomes. METHODS: We retrospectively reviewed patients at our institution who underwent LVAD implantation between April 2014 and August 2018. We evaluated the grade of TR by echocardiography before and after LVAD implantation. Moderate or greater TR was defined as significant. RESULTS: Among 199 consecutive patients, 194 had at least 2 echocardiographic TR assessments before and after LVAD implantation. Of these patients, 108 were included in the TVI-positive (TVI+) group and 86 in the TVI-negative (TVI-) group. In the TVI+ group, the prevalence of significant TR decreased from 52% to about 20% in the first 6 months after implantation (P < .01). Overall survival and HF readmission-free survival were comparable between the TVI+ and TVI- patients. In contrast, patients in both groups who had significant postoperative TR during early follow-up had worse 2-year HF readmission-free survival (36% in patients with significant postoperative TR vs 55% in those without significant postoperative TR; P = .028). CONCLUSIONS: Concomitant TVI with LVAD implantation improved TR in most patients but did not have an impact on clinical outcomes. Significant postoperative TR after LVAD implantation, in patients with and without TVI, was associated with worse HF-free outcomes.

Omega-3 and hemocompatibility-related adverse events.

BACKGROUND: Hemocompatibility-related clinical adverse events (HRAEs) are major causes of readmission in patients with left ventricular assist devices (LVADs). Omega-3 is an unsaturated fatty acid that possesses anti-inflammatory and antiangiogenic properties. We aimed to investigate the impact of omega-3 therapy on HRAEs during LVAD support. METHODS: Consecutive LVAD patients who were followed for 6 months were enrolled, and stratified by the use of omega-3. Freedom from any HRAEs and net burden of HRAEs, which was calculated by using a hemocompatibility score (using 4 escalating tiers of hierarchal severity to derive a total score for events), were compared between those with and without omega-3 therapy. RESULTS: Among 169 LVAD patients (57 years old and 124 males), 31 patients received 4 g/d of omega-3 therapy and 138 patients were in the control group. During the 6-month observational period, freedom from any HRAEs was 90% in the omega-3 group compared with 70% in the control group with a hazard ratio of 0.35 (95% confidence interval 0.11-0.87 and P = .042). The average hemocompatibility score in the omega-3 group was significantly lower compared with the control group (0.23 vs 0.91; P = .042), due to reduced Tier I scores (mild HRAE; P = .003) and Tier IIIB scores (severe HRAE; P < .001). The similar trends remained at propensity-matched populations. CONCLUSIONS: Omega-3 therapy was associated with reduced HRAEs including both bleeding and thromboembolic events in LVAD patients.

Echocardiographic evaluation of the effects of sacubitril-valsartan on vascular properties in heart failure patients.

Increased vascular stiffness is known to be an independent predictor of mortality in patients with heart failure with reduced ejection fraction (HFrEF). The effects of sacubitril-valsartan on vascular structure and function have not been systematically studied in this patient population. We hypothesized that aortic distensibility (AD) and fractional area change (AFAC), as assessed by 2D transthoracic echocardiography (TTE), would improve over time in HFrEF patients on sacubitril-valsartan therapy, due to the vasodilatory properties of the medication. We prospectively studied 30 patients with HFrEF (25 < EF < 40%) on optimal guideline-directed medical therapy who were subsequently started on sacubitril-valsartan. Patients underwent serial 2D TTE imaging at baseline, 3 and 6 months following therapy initiation. Ascending aortic diameters were measured 3 cm above the aortic valve in the parasternal long-axis view and used to calculate AD and AFAC, two markers of vascular compliance. For reference, we also measured AD and AFAC in 30 healthy, age and gender-matched controls at a single time point. Normal controls had significantly higher values of AD and AFAC than HFrEF patients at baseline (AD: 4.0 ± 1.1 vs. 2.2 ± 0.9 cm2dyne-110-3, p < 0.0001 and AFAC: 18.8 ± 3.7% vs. 10.3 ± 4.3%, p < 0.0001). In HFrEF patients on sacubitril-valsartan, both indices of aortic compliance progressively improved towards normal from baseline to 6 months: AD from 2.2 ± 0.9 to 3.6 ± 1.5 cm2dyne-110-3 (p < 0.0001) and AFAC from 10.3 ± 4.3 to 13.7 ± 4.1% (p < 0.0001). In conclusion, AD and AFAC are decreased in patients with HFrEF and gradually improve with sacubitril-valsartan treatment. The echocardiographic markers used in this study may become a useful tool to assess the effectiveness of sacubitril-valsartan therapy in HFrEF patients.

Estimation of the Severity of Aortic Insufficiency by HVAD Flow Waveform.

PURPOSE: Aortic insufficiency (AI) significantly affects morbidity and mortality in patients with left ventricular assist devices. Although AI may be commonly assessed by echocardiography, expert techniques are required for accurate quantification of AI severity. DESCRIPTION: In this prospective blinded study, screenshots from the HVAD (Medtronic, Framingham, MA) display and simultaneous echocardiographic measurements were obtained. Each screenshot was digitized and the early diastolic phase slope was calculated, with blinding to the echocardiographic results. The regurgitant fraction of AI was quantified by Doppler echocardiography of the outflow graft. EVALUATION: A total of 30 patients (median, 57 years old; 57% male) were enrolled. A cutoff of -17.6 L/min/s for the early diastolic phase slope had a sensitivity of 0.92 and a specificity of 0.53 to estimate significant AI with a regurgitant fraction of 30% or greater, and it significantly stratified patients into a low regurgitant faction group (0.3%) and a high regurgitant fraction group (33.0%) (P = .009). The early diastolic phase slope had a moderate correlation with the actually measured regurgitant fraction (r = .50). CONCLUSIONS: The early diastolic phase slope of the HVAD flow waveform may be a parameter that can estimate the presence of clinically significant AI.

Hemodynamics of concomitant tricuspid valve procedures at LVAD implantation.

BACKGROUND: Tricuspid regurgitation (TR) is common in patients receiving left ventricular assist device (LVAD) implantation. The current literature is conflicting regarding the effects of concomitant tricuspid valve repair (TVR) at LVAD implantation. We investigated the hemodynamic effects of concomitant TVR at LVAD implantation. METHODS: Consecutive clinically stable LVAD outpatients who underwent hemodynamic ramp testings were enrolled in this study, and they were stratified by concomitant TVR. Results of hemodynamic ramp tests were compared between the TVR group and the non-TVR group. RESULTS: Among 65 LVAD patients undergoing ramp tests, 34 patients had received TVR, and 31 had not. There were no significant differences in baseline characteristics between two groups except for higher degree of TR and lower pulmonary artery pulsatility index in the TVR group (P < .05 for both). Following LVAD implantation, the degree of TR improved significantly in the TVR group down to the comparable level with the non-TVR group. During ramp tests, the TVR group had steeper cardiac index slope (0.14 ± 0.12 vs 0.07 ± 0.07 L/min/m2 /step, P = .002) and higher cardiac index at set LVAD speed (2.99 ± 0.84 vs 2.52 ± 0.42 L/min/m2 , P = .007). CONCLUSIONS: Concomitant TVR improves cardiac output and its response to LVAD speed change following LVAD implantation. Longitudinal clinical implications of such hemodynamic changes are unknown.

Omega-3 Therapy Is Associated With Reduced Gastrointestinal Bleeding in Patients With Continuous-Flow Left Ventricular Assist Device.

Background Gastrointestinal bleeding (GIB) is a common complication seen in patients supported with left ventricular assist devices (LVADs) and is related to increased inflammation and angiogenesis. Omega-3 is an unsaturated fatty acid that possesses anti-inflammatory and antiangiogenic properties. This study aims to assess the prophylactic efficacy of treatment with omega-3 on the incidence of GIB in LVAD patients. Methods and Results Among consecutive 166 LVAD patients enrolled in this analysis, 30 patients (49 years old and 26 male) received 4 mg/d of omega-3 therapy for 310±87 days and 136 patients in the control group (58 years old and 98 male) were observed for 302±102 days. One-year GIB-free rate was significantly higher in the omega-3 group as compared with the control group (97% versus 73%; P=0.02). Omega-3 therapy was associated with the occurrence of GIB in both the univariate (hazard ratio, 0.12; 95% CI, 0.02-0.91; P=0.040) and multivariate Cox proportional hazard ratio analyses (hazard ratio, 0.13; 95% CI, 0.02-0.98; P=0.047). The frequency of GIB was significantly lower in the omega-3 group (0.08±0.42 versus 0.37±0.93 events/y; P=0.01), accompanied by significantly lower blood product transfusion and shorter days in the hospital. The frequency of GIB remained lower among the omega-3 group after matching for patient background characteristics (96% versus 73%, P=0.028). Conclusions LVAD patients treated with omega-3 had a significant increase in freedom from GIB. A randomized controlled study is warranted to evaluate the use of omega-3 in LVAD patients.