Interaction between ischemic time and donor age under the new donor heart allocation system: Effect on post-transplant survival.

BACKGROUND: Ischemic time (IT) under the new heart transplant (HTx) allocation system has increased compared to the old system. We investigated the effect of IT and donor age on post-HTx survival. METHODS: The United Network for Organ Sharing (UNOS) database was analyzed to identify adult HTx between October 2015 and August 2020. Recipients were stratified by donor age, transplantation era, and IT. Kaplan-Meier and log-rank tests were used to compare 180-day post-HTx mortality. Cox proportional hazards modeling and propensity score matching were performed to adjust for confounders. RESULTS: Under the new system (N = 3654), IT≥4 h led to decreased survival compared to IT < 4 h (91.4% vs. 93.7%; P = .02), although this decrease was undetectable among those with donors ≥39 years old (90.4% vs. 91.1%; P = .73). IT≥4 h led to decreased survival with donors < 39 years old (91.7% vs. 94.6%; P < .01). Under the old system (N = 5987), IT≥4 h resulted in decreased survival (89.8% vs. 93.9%; P < .01), including with donors ≥39 years old (86.9% vs. 92.4%; P < .01). CONCLUSIONS: IT≥4 h remains a risk for post-HTx mortality under the new system. However, the magnitude of this effect is blunted when donor age is ≥39 years, likely secondary to increased allocation of these organs to lower status, more stable recipients.

Using aortic arch short axis views during transesophageal echocardiographic examination facilitates right ventricular assist device imaging.

Given the increased need for mechanical circulatory support and subsequent development of right ventricular assist devices (RVAD), appropriate imaging needs to be described to facilitate care in patients with cardiogenic shock and heart failure. We present three cases in which the upper esophageal aortic arch short axis (UE AA SAX) view on transesophageal echocardiography (TEE) was utilized to effectively image RVADs: to confirm normal positioning, to detect and guide repositioning, and to visualize malfunction. These cases support the importance of the UE AA SAX TEE view in RVAD outflow imaging and, when obtainable, should be included in routine RVAD assessment.

MicroRNA-21 regulates right ventricular remodeling secondary to pulmonary arterial pressure overload.

Right ventricular (RV) function is a critical determinant of survival in patients with pulmonary arterial hypertension (PAH). While miR-21 is known to associate with vascular remodeling in small animal models of PAH, its role in RV remodeling in large animal models has not been characterized. Herein, we investigated the role of miR-21 in RV dysfunction using a sheep model of PAH secondary to pulmonary arterial constriction (PAC). RV structural and functional remodeling were examined using ultrasound imaging. Our results showed that post PAC, RV strain significantly decreased at the basal region compared with t the control. Moreover, such dysfunction was accompanied by increases in miR-21 levels. To determine the role of miR-21 in RV remodeling secondary to PAC, we investigated the molecular alteration secondary to phenylephrine induced hypertrophy and miR21 overexpression in vitro using neonatal rat ventricular myocytes (NRVMs). We found that overexpression of miR-21 in the setting of hypertrophic stimulation augmented only the expression of proteins critical for mitosis but not cytokinesis. Strikingly, this molecular alteration was associated with an eccentric cellular hypertrophic phenotype similar to what we observed in vivo PAC animal model in sheep. Importantly, this hypertrophic change was diminished upon suppressing miR-21 in NRVMs. Collectively, our in vitro and in vivo data demonstrate that miR-21 is a critical contributor in the development of RV dysfunction and could represent a novel therapeutic target for PAH associated RV dysfunction.

A meta-analysis of transcarotid versus transfemoral transcatheter aortic valve replacement.

BACKGROUND: Carotid access has shown promise as an excellent delivery route for transcatheter aortic valve replacement (TAVR). We aimed to compare outcomes of transcarotid (TC) and transfemoral (TF) TAVR by conducting a search and analysis of the best evidence in the literature to shed light on its safety and effectiveness. METHODS: The PubMed/MEDLINE, Embase, and Cochrane library from inception to July 2020 were searched to identify articles reporting comparative data on TC versus TF approaches for TAVR. Patients' baseline characteristics and clinical outcomes were extracted from the articles and pooled for analysis. RESULTS: Five studies, including a total of 2470 patients, were included in the study with 1859 patients in the TF group and 611 patients in the TC group. The TC group had higher prevalence of peripheral vascular disease, while the patients in the TF group was older. Meta-analysis revealed that there was no significant differences between the two groups with regard to 30-day mortality (p = 0.09), stroke (p = 0.28), new dialysis (p = 0.58), major bleeding (p = 0.69), or pacemaker implantation (p = 0.44). The TF group had a higher incidence of vascular complications (3.9% vs. 2.3%; OR 2.22; 95% CI [1.13, 4.38]; p = 0.02). CONCLUSIONS: Compared with the TF approach, TC-TAVR is associated with comparable procedural and clinical outcomes. Our analysis found a lower rate of vascular complication in TC access compared with TF access. This supports consideration of such an alternative access when there are concerns over the feasibility of TF access.

Untwist the twist: instant hemodynamic improvement in known HeartMate 3 complication.

The HeartMate 3 [HM3 (Abbott, Abbott Park, Illinois)] is a left-ventricular assist device (LVAD) with excellent clinical results. Outflow graft occlusion as a complication secondary to outflow graft twisting was reported to occur in 1.6% within the MOMENTUM 3 trial. The anti-twist metal clip or modified bend relief is made to prevent this complication currently, however, there remain large numbers of early implanted HM3 which may develop this complication. There are limited reports illustrating diagnosis, surgical repair, and post-repair hemodynamic changes of these complications. Thus, we present a case of successful diagnosis and surgical repair of an outflow graft twist. Simple procedure through thoracotomy without cardiopulmonary bypass provides significant immediate hemodynamic improvement.

Left thoracotomy vs full sternotomy for centrifugal durable LVAD implantation: 1-year outcome comparison post-LVAD and post-heart transplantation.

Left ventricular assist device (LVAD) implantations have traditionally been approached through a full median sternotomy (FS). Recently, a minimally invasive left thoracotomy (LT) approach has been popularized. This study sought to compare the outcomes of FS and LT patients post-primary LVAD implantation and post-subsequent heart transplant (HT). This was a single-center retrospective study. 83 patients who underwent primary centrifugal durable LVAD implantation from January 2014 to June 2018 were included (FS, n = 41; LT, n = 42). 41 patients had a subsequent HT (FS, n = 19; LT, n = 22). Pre-operative patient demographics, intraoperative variables, post-operative 1-year survival, length of hospital stay, complications, and outcomes for LVAD implantation and following HT were analyzed. Intraoperative data showed that the LT group had a 23.4% longer mean LVAD implant surgical time (p < 0.01). One-year post-LVAD survival was similar between the two groups (p = 0.05). Complication rates, with the exception of the rate of hemorrhagic stroke (p = 0.04) post-LVAD implant were similar. One-year survival post-HT was similar between groups (p = 0.35). Complication rates and mean length of hospital stay were also similar (p = 1.0) post-HT. Our study demonstrated that LT approach does not negatively affect post-LVAD implantation or post-HT outcomes. Further, larger studies may determine more detailed effects of LT approach.

Successful use of Impella 5.5 to manage cardiogenic shock complicated by COVID-19.

BACKGROUND: Acute decompensated heart failure in patients with coronavirus disease 2019 (COVID-19) is becoming increasingly common. AIMS: In this case report, we describe the successful use of an Impella 5.5 (Abiomed) to treat cardiogenic shock refractory to inotropic therapy. MATERIALS & METHODS: Transthoracic and transesophageal echocardiography confirmed severely diminished left ventricular ejection fraction and a reverse-transcription polymerase chain reaction test revealed that the patient was COVID-19 positive during his hospital admission. RESULTS: Following initiation of inotropic therapy, we placed an Impella 5.5 for further cardiac support. The patient's LVEF and cardiac index improved after 21 days on the Impella 5.5 and was maintained following explant. DISCUSSION & CONCLUSION: The findings reported here demonstrate successful use of an Impella 5.5 to improve native heart function in refractory cardiogenic shock and further indicate its use as an option for those in acute decompensated heart failure who have tested positive for COVID-19 infection.

Plasma Proteomic Profiling in Hypertrophic Cardiomyopathy Patients before and after Surgical Myectomy Reveals Post-Procedural Reduction in Systemic Inflammation.

Left Ventricular Outflow Tract (LVOT) obstruction occurs in approximately 70% of Hypertrophic Cardiomyopathy (HCM) patients and currently requires imaging or invasive testing for diagnosis, sometimes in conjunction with provocative physiological or pharmaceutical stimuli. To identify potential biomarkers of LVOT obstruction, we performed proteomics profiling of 1305 plasma proteins in 12 HCM patients with documented LVOT obstruction, referred for surgical myectomy. Plasma was collected at the surgical preoperative visit, approximately one month prior to surgery and then at the post-surgical visit, approximately 3 months later. Proteomic profiles were generated using the aptamer-based SOMAscan assay. Principal Component Analysis using the highest statistically significant proteins separated all preoperative samples from all postoperative samples. Further analysis revealed a set of 25 proteins that distinguished the preoperative and postoperative states with a paired t-test p-value of <0.01. Ingenuity Pathway analysis facilitated the generation of protein interaction networks and the elucidation of key upstream regulators of differentially expressed proteins, such as interferon-γ, TGF-ß1, and TNF. Biological pathways affected by surgery included organ inflammation, migration, and motility of leukocytes, fibrosis, vasculogenesis, angiogenesis, acute coronary events, endothelial proliferation, eicosanoid metabolism, calcium flux, apoptosis, and morphology of the cardiovascular system. Our results indicate that surgical relief of dynamic outflow tract obstruction in HCM patients is associated with unique alterations in plasma proteomic profiles that likely reflect improvement in organ inflammation and physiological function.

A case series: the outcomes, support duration, and graft function recovery after VA-ECMO use in primary graft dysfunction after heart transplantation.

Primary graft dysfunction (PGD) is a rare complication associated with high mortality after heart transplantation, which may require veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) support. A standardized definition for PGD was developed by the International Society of Heart and Lung Transplantation in 2014. Due to limited reports using this definition, the detailed outcomes after VA-ECMO support remain unclear. Therefore, we retrospectively analyzed our single-center outcomes of PGD following VA-ECMO support. Between September 2014 and August 2018, 160 patients underwent heart transplantation in our single center. Nine PGD patients required VA-ECMO support, with an incidence of 5.6%. Pre-operative recipient/donor demographics, intra-operative variables, timing of VA-ECMO initiation and support duration, graft function recovery during 30 days after heart transplant, VA-ECMO complications, and survival were analyzed. The indication for VA-ECMO support was biventricular failure for all nine patients. Six patients had severe PGD requiring intra-operative VA-ECMO, while two patients had moderate PGD and one patient had mild PGD requiring post-operative VA-ECMO. All cohorts were successfully decannulated in a median of 10 days. Survival to discharge rate was 88.9%. One-year survival rate was 85.7%. Left ventricular ejection fraction recovered to normal within 30 days in all PGD patients. Our study showed VA-ECMO support led to high survival and timely graft function recovery in all cohorts. Further larger research can clarify the detailed effects of VA-ECMO support which may lead to standardized indication of VA-ECMO support for PGD patients.

The Impact of Pre-Heart Transplantation Blood Transfusion Varies Based on Recipient MELD-XI Score.

Prior studies reveal adverse effects of transfusion on cardiac surgery, but little is known of transfusion impact on heart transplantation. First-time, single-organ adult heart transplant recipients between January 1, 2010, and December 31, 2020, were included, stratified above or below a model for end-stage liver disease excluding international normalized ratio (MELD-XI) score of 9.4, and propensity score matched to their nearest neighbor. A 90 day landmark analysis within each cohort was also performed. Unadjusted analysis showed transfusion recipients, MELD-XI ≥9.4, were more likely to experience post-heart transplantation mortality (Hazard Ratio (HR), 1.352 [95% Confidence Interval (CI), 1.239-1.477], p < 0.001), persisting after adjustment for potential confounders (adjusted HR, 1.211 [95% CI, 1.100-1.335], p < 0.001) and after propensity-score matching (HR, 1.174 [95% CI, 1.045-1.319], p = 0.007). Post-transplant length of stay was longer (25.9 vs. 23.2 days, p < 0.001). Post-transplant dialysis was more common (18.7 vs. 15.9%, p = 0.009). There was no survival difference on 90 day landmarked analysis (p = 0.108). With MELD-XI <9.4, there was slight survival detriment among transfusion recipients on univariable analysis (HR, 1.111 [95% CI, 1.001-1.234], p = 0.049) but not on multivariable analysis (adjusted HR, 1.061 [95% CI, 0.952-1.181], p = 0.285). There was similar survival after propensity-score matching (HR, 1.032 [95% CI, 0.903-1.180], p = 0.642) and on landmark analysis (p = 0.581). Ultimately, transfusion was associated with worse post-heart transplantation outcomes among recipients with a MELD-XI ≥9.4.

Blood type O heart transplant candidates have longer waitlist time and higher delisting under the new allocation system.

OBJECTIVE: Prior studies have examined the effect of blood type on heart transplantation (HTx) waitlist outcomes in cohorts through 2015. We aim to analyze the effect of blood type on contemporary waitlist outcomes with a new allocation system focus. METHODS: Adults listed for HTx between April 2015 and December 2020 were included. Survival to HTx and waitlist death/deterioration was compared between type O and non-type O candidates using competing risks regression. Donor/recipient ABO compatibility trends were further investigated. RESULTS: Candidates with blood type O (n = 7509) underwent HTx less frequently than candidates with blood type other than type O (n = 9699) (subhazard ratio [sHR], 0.56; 95% CI, 0.53-0.58) with higher rates of waitlist death/deterioration (sHR, 1.18; 95% CI, 1.04-1.34). Subgroup analyses demonstrated persistence of this trend under the new donor heart allocation system (HTx: sHR, 0.58; 95% CI, 0.54-0.62; death/clinical deterioration: sHR, 1.27; 95% CI, 1.02-1.60), especially among those listed at high status (1, 2, or 3) (HTx: sHR, 0.69; 95% CI, 0.63-0.75; death/deterioration: sHR, 1.61; 95% CI, 1.16-2.22). Among those listed at status 3, waitlist death/deterioration was modified by presence of a durable left ventricular assist device (left ventricular assist device: sHR, 1.57; 95% CI, 0.58-4.29; no left ventricular assist device: sHR, 3.79; 95% CI, 1.28-11.2). Type O donor heart allocation to secondary ABO candidates increased in the new system (14.5% vs 12.0%; P < .01); post-HTx survival remained comparable between recipients with blood type O and non-type O (log-rank P = .07). CONCLUSIONS: Further logistical considerations are warranted to minimize allocation inequity regarding blood type under the new allocation system.

Donor Age More Than 20 Years Greater Than Recipient Age Is Associated With Worse 5 Year Survival in Young Adult Heart Transplantation.

Prior studies indicate donor age-recipient age (DA-RA) difference may be of prognostic value in adolescents, although not adults. We aim to analyze the relationship between DA-RA difference and long-term survival of young adult heart transplantation (HTx) recipients. First-time, single-organ HTx recipients aged 18-30 who underwent HTx between 2010 and 2020 were analyzed from the United Network for Organ Sharing (UNOS) registry. Four cohorts were created based on DA-RA difference. The primary outcome was 5 year post-HTx survival. Secondary outcome was post-HTx complications. One thousand eight hundred three donor-recipient pairs were divided into four groups: DA-RA < 0, 0 ≤ DA-RA < 10, 10 ≤ DA-RA < 20, and DA-RA ≥ 20 with 682 (37.8%), 651 (36.1%), 356 (19.7%), 114 (6.3%) pairs in each cohort, respectively. The estimated 5 year survival of the DA-RA ≥ 20 cohort was 66.5% compared to the other three groups at ~75%. After adjustment, DA-RA ≥ 20 was independently associated with worse survival compared to DA-RA < 0 (adjusted hazard ratio [HR] = 1.55; 95% confidence interval [CI] = 1.06-2.27; log-rank p = 0.008). There was no significant difference in complication incidence across cohorts. Among young adults, accepting a donor heart more than 20 years older than the recipient was associated with worse 5 year survival. We did not detect a significant difference up to 20 years. This information may help guide appropriate donor selection in the young adult population.

True external diameter better predicts hemodynamic performance of bioprosthetic aortic valves than the manufacturers' stated size.

BACKGROUND AND AIM OF THE STUDY: Currently, there is no universal standard for sizing bioprosthetic aortic valves. Hence, a standardized comparison was performed to clarify this issue. METHODS: Every size of four commercially available bioprosthetic aortic valves marketed in the United States (Biocor Supra; Mosaic Ultra; Magna Ease; Mitroflow) was obtained. Subsequently, custom sizers were created that were accurate to 0.0025 mm to represent aortic roots 18 mm through 32 mm, and these were used to measure the external diameter of each valve. Using the effective orifice area (EOA) and transvalvular pressure gradient (TPG) data submitted to the FDA, a comparison was made between the hemodynamic properties of valves with equivalent manufacturer stated sizes and valves with equivalent measured external diameters. RESULTS: Based on manufacturer size alone, the valves at first seemed to be hemodynamically different from each other, with Mitroflow valves appearing to be hemodynamically superior, having a large EOA and equivalent or superior TPG (p < 0.05). However, Mitroflow valves had a larger measured external diameter than the other valves of a given numerical manufacturer size. Valves with equivalent external diameters were then compared, regardless of the stated manufacturer sizes. For truly equivalently sized valves (i.e., by measured external diameter) there was no clear hemodynamic difference. There was no statistical difference in the EOAs between the Biocor Supra, Mosaic Ultra, and Mitroflow valves, and the Magna Ease valve had a statistically smaller EOA (p < 0.05). On comparing the mean TPG, the Biocor Supra and Mitroflow valves had statistically equivalent gradients to each other, as did the Mosaic Ultra and Magna Ease valves. CONCLUSION: When comparing valves of the same numerical manufacturer size, there appears to be a difference in hemodynamic performance across different manufacturers' valves according to FDA data. However, comparing equivalently measured valves eliminates the differences between valves produced by different manufacturers.

The Use of Impella 5.5 for Donor-Heart Hemodynamic Support in Heart Transplantation.

Primary graft dysfunction is a feared complication and cause of mortality post-heart transplant. Primary graft dysfunction may require mechanical circulatory support, such as venoarterial extracorporeal membrane oxygenation, which carries its own risk for complications. We developed a new mechanical circulatory support method for patients who underwent heart transplant bridged with Impella 5.5, which was then placed into the donor heart. Among 12 heart transplants, four required Impella 5.5 support. The average age was 55.8 years. The mean duration for postoperative mechanical circulatory support was 3.8 days, ranging from 2 to 5 days. No patients developed severe right ventricular dysfunction. In our limited study, complications and mortality associated with the replanted Impella 5.5 were both 0%.

Use of Mechanical Circulatory Support to Demonstrate Pulmonary Hypertension Reversibility in Mitral Stenosis.

A 56 year old female with a history of rheumatic mitral stenosis (MS) presented with severe pulmonary edema. Transthoracic echocardiogram demonstrated severe MS (mean valve area 0.5 cm 2 , mean gradient of 16 mm Hg) with preserved left ventricular ejection fraction. Right heart catheterization demonstrated elevated pulmonary artery (PA) pressures of 110/80 mm Hg and a wedge pressure of 40 mm Hg. Mechanical circulatory support (MCS) was initiated with extracorporeal left atrial to femoral artery bypass. MCS allowed preoperative unloading of the left atrium. The volume status and lung congestion were optimized before surgery. In addition, pulmonary hypertension reversibility was demonstrated with significantly lower PA pressures after initiation of MCS. Intraoperatively, the MCS left atrial inflow cannula was pulled back into the right heart and used as a venous cannula for cardiopulmonary bypass. Successful mitral valve replacement was performed. Postoperatively, the mitral valve mean gradient was 3 mm Hg.