Current Status of Cardiac Regenerative Therapy Using Induced Pluripotent Stem Cells.

Heart failure (HF) is a life-threatening disorder and is treated by drug therapies and surgical interventions such as heart transplantation and left ventricular assist device (LVAD). However, these treatments can lack effectiveness in the long term and are associated with issues such as donor shortage in heart transplantation, and infection, stroke, or gastrointestinal bleeding in LVADs. Therefore, alternative therapeutic strategies are still needed. In this respect, stem cell therapy has been introduced for the treatment of HF and numerous preclinical and clinical studies are employing a range of stem cell varieties. These stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), have been shown to improve cardiac function and attenuate left ventricular remodeling. IPSCs, which have a capacity for unlimited proliferation and differentiation into cardiomyocytes, are a promising cell source for myocardial regeneration therapy. In this review, we discuss the following topics: (1) what are iPSCs; (2) the limitations and solutions for the translation of iPSC-CMs practically; and (3) the current therapeutic clinical trials.

Transmural macrophage migration into an arterial bioresorbable vascular graft promotes inflammatory-mediated response and collagen deposition for vascular remodeling.

Macrophages are the primary cell type orchestrating bioresorbable vascular graft (BVG) remodeling and infiltrate from three sources: the adjacent native vessel, circulating blood, and transmural migration from outer surface of the graft. To elucidate the kinetics of macrophage infiltration into the BVG, we fabricated two different bilayer arterial BVGs consisting of a macroporous sponge layer and a microporous electrospun (ES) layer. The Outer ES graft was designed to reduce transmural cell infiltration from the outer surface and the Inner ES graft was designed to reduce cell infiltration from the circulation. These BVGs were implanted in mice as infrarenal abdominal aorta grafts and extracted at 1, 4, and 8 weeks (n = 5, 10, and 10 per group, respectively) for evaluation. Cell migration into BVGs was higher in the Inner ES graft than in the Outer ES graft. For Inner ES grafts, the majority of macrophage largely expressed a pro-inflammatory M1 phenotype but gradually changed to tissue-remodeling M2 macrophages. In contrast, in Outer ES grafts macrophages primarily maintained an M1 phenotype. The luminal surface endothelialized faster in the Inner ES graft; however, the smooth muscle cell layer was thicker in the Outer ES graft. Collagen fibers were more abundant and matured faster in the Inner ES graft than that in the Outer ES graft. In conclusion, compared to macrophages infiltrating from the circulating blood, transmural macrophages from outside promote the acute inflammatory-mediated response for vascular remodeling and subsequent collagen deposition within BVGs. STATEMENT OF SIGNIFICANCE: To elucidate the kinetics of macrophage infiltration into the bioresorbable vascular graft (BVG), two different bilayer arterial BVGs were implanted in mice as infrarenal abdominal aorta grafts. Cell migration into BVGs was higher in the inner electrospun graft which cells mainly infiltrate from outer surface than in the outer electrospun graft which cells mainly infiltrate from the circulating blood. In the inner electrospun grafts, the majority of macrophages changed from the M1 phenotype to the M2 phenotype, however, outer electrospun grafts maintained the M1 phenotype. Collagen fibers matured faster in the Inner electrospun graft. Compared to macrophages infiltrating from the circulating blood, transmural macrophages from outside promote the acute inflammatory-mediated response for vascular remodeling and subsequent collagen deposition within BVGs.

Acute Hemodynamic Compromise After Transcatheter Aortic Valve Replacement Due to Dynamic Left Ventricle Obstruction: A Systematic Review.

Acute hemodynamic compromise after transcatheter aortic valve replacement (TAVR) because of dynamic left ventricle (LV) obstruction (LVO), also known as suicide LV, is an infrequent but severe complication of TAVR that is poorly defined in previous studies. Understanding this complication is essential for its prompt diagnosis and optimal treatment. We conducted a systematic literature review using PubMed, Embase, Web of Science, and Medline databases for studies describing acute hemodynamic compromise after TAVR because of dynamic LVO or suicide LV. Each study was reviewed by 2 authors individually for eligibility, and a third author resolved disagreements. From a total of 506 studies, 25 publications were considered for the final analysis. The majority of patients with this condition were women demonstrating a hypertrophic septum, a small ventricle, and hyperdynamic contractility on pre-TAVR echocardiographic assessment. An intraventricular gradient before TAVR was found in half of the cases. Acute hemodynamic compromise after TAVR because of dynamic LVO manifested mainly as significant hypotension and occurred most often immediately after valve deployment. The LV outflow tract was the most common site of obstruction. Advanced therapies were required in nearly 65% of the cases. In conclusion, acute hemodynamic compromise after TAVR because of dynamic LVO occurred almost invariably in women. Echocardiography before TAVR may offer essential information to anticipate this complication. LV outflow tract obstruction appears to carry the highest risk of developing this phenomenon. Advanced therapies should be promptly considered as a bailout strategy in patients with hemodynamic collapse refractory to medical therapy.

3-dimensional intracardiac echocardiography for structural heart interventions.

New generation 3-dimensional matrix array intracardiac echocardiography catheters have become commercially available recently, increasing image plane options compared to 2-dimensional and older generation 3-dimensional intracardiac echocardiography catheters. They are beginning to play an important role in structural heart interventions, especially for transcatheter tricuspid interventions, due to advantages in some situations that increase image quality over transesophageal echocardiography.

Vascular access for transcatheter aortic valve replacement: A network meta-analysis.

BACKGROUND: The choice of an alternative access for transcatheter aortic valve replacement (TAVR) remains controversial when transfemoral (TF) access is not feasible. METHODS: We conducted a network meta-analysis to compare the outcomes of TAVR via various peripheral vascular accesses. MEDLINE and EMBASE were searched through July 2022 to identify studies that investigated outcomes in patients who underwent TAVR via TF, trans-subclavian (Tsc), transcarotid (TC), or transcaval (Tcav) access. A network meta-analysis was conducted via random-effects model. Outcomes of interest were major or life-threatening bleeding, stroke, major vascular complication, and 30-day mortality. RESULTS: No randomized trial was identified. Our analysis included 33 observational studies that enrolled a total of 43,455 patients who underwent TAVR via TF (n = 36,202), Tsc (n = 3869), TC (n = 3066), or Tcav (n = 318) access. The risk of major or life-threatening bleeding was higher via Tsc compared with TF [odds ratio (OR); 95 % confidence interval (CI) =1.51 (1.03-2.23), p = 0.034]. The risk of stroke was higher via Tsc compared with TF and Tcav [OR (95 % CI) =2.00 (1.14-3.52), p = 0.018, OR (95 % CI) =2.43 (1.03-5.74), p = 0.044, respectively]. The risk of major vascular complications was lower via TC compared with Tsc, and Tcav and higher with Tcav compared with TF and Tsc. 30-day mortality was higher via Tsc compared with TF. Tsc was associated with higher risk of major or life-threatening bleeding compared with TF, and higher risk of stroke compared to TF and Tcav. Tcav had the highest risk of major vascular complications. CONCLUSION: In patients who underwent TF, Tsc, TC, or Tcav TAVR, Tsc had a higher rate of stroke compared to TF and Tcav, and major or life-threatening bleeding compared to TF. The rate of major vascular complications in Tcav was the highest among the four approaches.

Selection of Vascular Closure Devices in Transcatheter Aortic Valve Replacement: Systematic Review and Network Meta-Analysis.

Various vascular closure devices (VCDs) are commonly used for percutaneous transcatheter aortic valve replacement (TAVR). However, superiority and safety profile among them remain unclear. We compared periprocedural complications among various VCDs in patients undergoing TAVR. PubMed and EMBASE were searched through January 2022 to identify clinical studies comparing any 2 VCDs of Prostar, Proglide and MANTA in patients who underwent TAVR. Studies using surgical cut-down or alternative access other than transfemoral approach were excluded. We analyzed the odds ratios (ORs) of vascular complications (VC), bleeding, acute kidney injury and all-cause mortality using a network meta-analysis. All outcomes were defined by Valve Academic Research Consortium 2 criteria. Two randomized controlled trials and 15 observational studies were identified, yielding a total of 11,344 patients including Prostar (n = 4499), Proglide (n = 5705), or MANTA group (n = 1140). The rates of major VC and life-threatening and major bleeding were significantly lower in Proglide compared to Prostar (OR [95 % CI] = 0.54 [0.32-0.89], 0.68 [0.52-0.90], and 0.49 [0.26-0.95], respectively). There was no significant difference in major VC and bleeding between Proglide and MANTA groups. Proglide was associated with a lower rate of acute kidney injury (0.56 [0.34-0.92]) and red blood cell transfusion (0.39 [0.16-0.98]) compared to Prostar. There was no significant difference in additional interventions and 30-day overall mortality among three groups. In this network meta-analysis of VCD in patients undergoing TAVR, MANTA and Proglide had comparable outcomes while Proglide appears superior to Prostar in terms of major VC and bleeding.

Continuous-Flow Left Ventricular Assist Device Therapy in Adults with Transposition of the Great Vessels.

An increasing number of children with congenital heart disease are surviving into adulthood and subsequently developing end-stage heart failure. Two example populations are adults who have been previously operated on for congenitally corrected transposition of the great arteries (CCTGA) and transposition of the great arteries (TGA). Implantation of a continuous flow left ventricular assist device (CF-LVAD) in these patients can present unusual anatomical and physiologic challenges. In this report, we describe outcomes of CF-LVAD implantation in three such patients. These cases demonstrate the feasibility of implanting a CF-LVAD in patients who have undergone surgery for CCTGA and/or TGA.

Left Ventricular Recovery with Explantation of Continuous-Flow Left Ventricular Assist Device after 5 Years of Support.

Mechanical circulatory support may result in sufficient myocardial recovery to allow for explantation of the left ventricular assist device (LVAD). The duration of support associated with left ventricular recovery has generally been 6-12 months. In this report, we present a patient in whom the left ventricle recovered after 5 years of support with a LVAD. Our report demonstrates that long-term monitoring for left ventricular recovery is prudent and may allow for late device explantation.

The evaluation of a tissue-engineered cardiac patch seeded with hips derived cardiac progenitor cells in a rat left ventricular model.

BACKGROUND: Ventricular septal perforation and left ventricular aneurysm are examples of potentially fatal complications of myocardial infarction. While various artificial materials are used in the repair of these issues, the possibility of associated infection and calcification is non-negligible. Cell-seeded biodegradable tissue-engineered patches may be a potential solution. This study evaluated the feasibility of a new left ventricular patch rat model to study neotissue formation in biodegradable cardiac patches. METHODS: Human induced pluripotent stem cell-derived cardiac progenitor cells (hiPS-CPCs) were cultured onto biodegradable patches composed of polyglycolic acid and a 50:50 poly (l-lactide-co-ε-caprolactone) copolymer for one week. After culturing, patches were implanted into left ventricular walls of male athymic rats. Unseeded controls were also used (n = 10/group). Heart conditions were followed by echocardiography and patches were subsequently explanted at 1, 2, 6, and 9 months post-implantation for histological evaluation. RESULT: Throughout the study, no patches ruptured demonstrating the ability to withstand the high pressure left ventricular system. One month after transplantation, the seeded patch did not stain positive for human nuclei. However, many new blood vessels formed within patches with significantly greater vessels in the seeded group at the 6 month time point. Echocardiography showed no significant difference in left ventricular contraction rate between the two groups. Calcification was found inside patches after 6 months, but there was no significant difference between groups. CONCLUSION: We have developed a surgical method to implant a bioabsorbable scaffold into the left ventricular environment of rats with a high survival rate. Seeded hiPS-CPCs did not differentiate into cardiomyocytes, but the greater number of new blood vessels in seeded patches suggests the presence of cell seeding early in the remodeling process might provide a prolonged effect on neotissue formation. This experiment will contribute to the development of a treatment model for left ventricular failure using iPS cells in the future.

Spontaneous reversal of stenosis in tissue-engineered vascular grafts.

We developed a tissue-engineered vascular graft (TEVG) for use in children and present results of a U.S. Food and Drug Administration (FDA)-approved clinical trial evaluating this graft in patients with single-ventricle cardiac anomalies. The TEVG was used as a Fontan conduit to connect the inferior vena cava and pulmonary artery, but a high incidence of graft narrowing manifested within the first 6 months, which was treated successfully with angioplasty. To elucidate mechanisms underlying this early stenosis, we used a data-informed, computational model to perform in silico parametric studies of TEVG development. The simulations predicted early stenosis as observed in our clinical trial but suggested further that such narrowing could reverse spontaneously through an inflammation-driven, mechano-mediated mechanism. We tested this unexpected, model-generated hypothesis by implanting TEVGs in an ovine inferior vena cava interposition graft model, which confirmed the prediction that TEVG stenosis resolved spontaneously and was typically well tolerated. These findings have important implications for our translational research because they suggest that angioplasty may be safely avoided in patients with asymptomatic early stenosis, although there will remain a need for appropriate medical monitoring. The simulations further predicted that the degree of reversible narrowing can be mitigated by altering the scaffold design to attenuate early inflammation and increase mechano-sensing by the synthetic cells, thus suggesting a new paradigm for optimizing next-generation TEVGs. We submit that there is considerable translational advantage to combined computational-experimental studies when designing cutting-edge technologies and their clinical management.

Sternum-Sparing HVAD Implantation with Attachment of the Outflow Graft to the Descending Aorta.

The standard approach for implanting an HVAD left ventricular assist device (LVAD) is performing a median sternotomy and sewing the outflow graft to the ascending aorta. However, in patients with sternal comorbidities, it may be advantageous to use a sternum-sparing approach. We retrospectively studied eight patients who underwent HVAD implantation for destination therapy via a left subcostal or fifth/sixth intercostal space incision. With this procedure, the outflow graft was sewed to the descending aorta. Ninety-day and one-year survival rates were 87.5% and 75%, respectively. Two patients (25%) died during the perioperative period: one from multisystem organ failure and the other from unrelated causes. We adjusted the HVAD speed to open the aortic valve once every three to four beats. Compared with other continuous-flow LVAD implantations performed at our institution during the study period (n = 437), this technique resulted in shorter bypass times and a lower incidence of infection; it was not associated with an increased incidence of heart failure, aortic root thrombosis, pump thrombosis, progression of aortic insufficiency, or ischemic neurologic dysfunction. Our findings suggest that a sternum-sparing approach for HVAD implantation is feasible and may be a safe option in patients with serious comorbidities that preclude the use of traditional implantation techniques.

Imatinib attenuates neotissue formation during vascular remodeling in an arterial bioresorbable vascular graft.

BACKGROUND: Bioresorbable vascular grafts (BVGs) can transform biologically into active blood vessels and represent an alternative to traditional synthetic conduits, which are prone to complications such as infection and thrombosis. Although platelet-derived growth factors and c-Kit positive cells play an important role in smooth muscle cell (SMC) migration and proliferation in vascular injury, atherosclerosis, or allograft, their roles in the vascular remodeling process of an arterial BVG remains unknown. Thus, we assessed the neottisue formation on arterial BVG remodeling by administrating imatinib, which is both a platelet-derived growth factor receptor kinase inhibitor and c-Kit receptor kinase inhibitor, in a murine model. METHODS: BVGs were composed of an inner poly(L-lactic-co-ε-caprolactone) copolymer sponge layer and an outer electrospun poly(L-lactic acid) nanofiber layer, which were implanted into the infrarenal abdominal aortas of C57BL/6 mice. After graft implantation, saline or 100 mg/kg of imatinib was administrated intraperitoneally daily for 2 weeks (n = 20 per group). Five mice in each group were scheduled to be humanely killed at 3 weeks and 15 at 8 weeks, and BVGs were explanted for histologic assessments. RESULTS: Graft patency during the 8-week observational period was not significantly different between groups (control, 86.7% vs imatinib, 80.0%; P > .999). Neotissue formation consisting of endothelialization, smooth muscle proliferation, and deposition of collagen and elastin was not observed in either group at 3 weeks. Similar endothelialization was achieved in both groups at 8 weeks, but thickness and percent area of neotissue formation were significantly higher in the control group than in the imatinib group, (thickness, 30. 1 ± 7.2 µm vs 19.6 ± 4.5 µm [P = .001]; percent area, 9.8 ± 2.7% vs 6.8 ± 1.8% [P = .005]). Furthermore, SMC layer and deposition of collagen and elastin were better organized at 8 weeks in the control group compared with the imatinib group. The thickness of SMC layer and collagen fiber area were significantly greater at 8 weeks in the control group than in the imatinib group (P < .001 and P = .026, respectively). Because there was no difference in the inner diameter of explanted BVGs (831.7 ± 63.4 µm vs 841.8 ± 41.9 µm; P = .689), neotissue formation was thought to advance toward the outer portion of the BVG with degradation of the polymer scaffold. CONCLUSIONS: Imatinib attenuates neotissue formation during vascular remodeling in arterial bioresorbable vascular grafts (BVGs) by inhibiting SMC layer formation and extracellular matrix deposition. CLINICAL RELEVANCE: This study demonstrated that imatinib attenuated neotissue formation during vascular remodeling in arterial Bioresorbable vascular graft (BVG) by inhibiting smooth muscle cell formation and extracellular matrix deposition. In addition, as imatinib did not modify the inner diameter of BVG, neotissue advanced circumferentially toward the outer portion of the neovessel. Currently, BVGs have not yet been clinically applied to the arterial circulation. The results of this study are helpful for the design of BVG that can achieve an optimal balance between polymer degradation and neotissue formation.

Gastrointestinal Bleeding After HeartMate II or HVAD Implantation: Incidence, Location, Etiology, and Effect on Survival.

The number of patients on destination therapy is increasing as long-term survival on continuous-flow left ventricular assist device (CF-LVAD) therapy has improved. Gastrointestinal bleeding (GIB) is a common complication after CF-LVAD implantation, and its risk correlates with longer support time, emphasizing the importance of GIB management. The lower pulsatility of CF-LVADs may promote arteriovenous malformations, which amplify the bleeding risk. Here, we retrospectively analyzed the location, incidence, and survival effect of GIB events in HeartMate II (HM-II) and HeartWare Ventricular Assist Device (HVAD) recipients to provide specific details regarding these complications. From November 2003 to March 2016, 526 patients with chronic heart failure underwent primary implantation of an HM-II (n = 403) or HVAD (n = 123) CF-LVAD at our center. Of the 526 patients, 140 (26.6%) had a GIB event (HM-II: n = 100; HVAD: n = 40), 92 (17.5%) had a single GIB event, and 48 (9.1%) had multiple GIB events (range: 2-9 events). HVAD recipients had a higher incidence of both upper and lower GIB events (p < 0.001 and P = 0.002, respectively) than HM-II recipients. Arteriovenous malformation was the most common etiology for GIB (50 patients/72 events); for this group, the average time-to-event was 300.4 days, the recurrence rate was 34%, and the 90-day and 1-year survival rates were 88.3% and 66.7%, respectively. Age at implantation was the only predictor of GIB. In conclusion, our study provides detailed information about GIB events associated with current CF-LVADs. Additional studies are required to evaluate strategies to reduce the incidence of GIB morbidity.

Outcomes in patients who underwent a concomitant tricuspid valve procedure during left ventricular assist device implantation.

BACKGROUND: Study findings have been inconsistent regarding whether a concomitant tricuspid valve replacement or repair performed concurrently with continuous-flow left ventricular assist device (CF-LVAD) implantation has additive clinical benefit in patients with severe tricuspid valve regurgitation (TR). AIM OF STUDY: To determine the effect of performing a concomitant tricuspid valve procedure (TVP) at the time of CF-LVAD implantation on patient outcomes. METHODS: We retrospectively reviewed our single-institution experience in 526 patients who underwent primary implantation of a CF-LVAD between November 2003 and March 2016. We identified 59 (11.2%) patients who had severe TR at the time of implantation and analyzed the effect of performing a concomitant TVP at the time of CF-LVAD implantation on the rate of survival, incidence of postoperative right heart failure (RHF), recurrence of TR, and incidence of 30-day readmission. RESULTS: We did not observe a significant difference in the overall survival rate (P = .51), incidence of postoperative RHF (P = .26), or recurrence of TR (P = .73) between patients with severe TR who underwent a TVP and those who did not at the time of CF-LVAD implantation. However, the incidence of 30-day readmission was significantly lower in patients who underwent a TVP than in those who did not (P = .002). CONCLUSIONS: Performing a concomitant TVP at the time of CF-LVAD implantation did not improve patient outcomes but reduced the incidence of 30-day readmission.

Device exchange from Heartmate II to HeartWare HVAD.

BACKGROUND: Despite technological advancements, pump durability and pump-related complications continue to affect and adversely impact the lives of patients with end-stage heart failure on left ventricular assist device (LVAD) support. In an attempt to avoid recurrent LVAD-related complications, there may be circumstances where it is clinically advantageous to exchange a patient's device from HeartMate II to HeartWare HVAD. However, there is a paucity of data that describes the safety and feasibility of such an approach. OBJECTIVE: We present the largest single-center series of HeartMate II (HMII) to HeartWare (HVAD) device exchanges. METHODS: A retrospective review of 11 patients who underwent HMII to HVAD exchange from 2012 to 2017 was conducted to evaluate patient characteristics, incidence of postoperative complications, and survival. RESULTS: Eleven male patients (mean age 55 ± 14.4 years) underwent HMII to HVAD device exchange. One patient expired on postoperative day 7 secondary to sepsis. One patient was lost-to-follow-up after 23 months. An additional three patients died at 5, 7, and 24 months. Mean follow-up after device exchange was 1555 ± 311 days for the remaining six patients. None of the 11 study patients underwent LVAD explant, further device exchange, or heart transplant. CONCLUSION: Exchange of an HMII LVAD to an HVAD can be performed safely with acceptable perioperative morbidity and mortality.

Concomitant valve procedures in patients undergoing continuous-flow left ventricular assist device implantation: A single-center experience.

OBJECTIVE: Long-term support with continuous-flow left ventricular assist devices (CF-LVADs) has improved the outcomes of patients with end-stage heart failure. However, valve disease management in patients who undergo CF-LVAD implantation remains controversial. The aim of this study was to assess our single-center experience with patients who underwent a concomitant valve procedure during implantation of a CF-LVAD. METHODS: From November 2003 through March 2016, 526 patients underwent primary CF-LVAD implantation with a HeartMate II (St Jude Inc, St Paul, Minn; n = 403) or HeartWare (Medtronic, Minneapolis, Minn; n = 123) device at our center. Of those, 91 underwent a concomitant valve procedure during implantation (CF-LVAD+valve procedure group), whereas 435 did not (CF-LVAD-only group). We compared preoperative characteristics and short-term and mid-term survival rates between these groups. RESULTS: The concomitant valve procedures performed included 13 tricuspid valve repairs, 19 aortic valve repairs or replacements, 30 mitral valve repairs or replacements, and 29 double valve repairs or replacements. Survival rates at 1 month, 6 months, 12 months, and 24 months were 90.3%, 81.4%, 74.9%, and 67.4%, respectively, for the CF-LVAD-only group and 89.0%, 75.8%, 70.3%, and 65.9%, respectively, for the CF-LVAD+valve procedure group (P = .55). The results of Cox regression multivariable modeling showed that performing a concomitant valve procedure was not an independent predictor of mortality (hazard ratio, 1.29; 95% confidence interval, 0.96-1.74; P = .08). CONCLUSIONS: In our experience, performing a concomitant valve procedure during CF-LVAD implantation was not associated with an increased mortality rate. The decision to perform a concomitant valve procedure should be made primarily on the basis of clinical indications for the procedure.

Severe LVAD-related infections requiring surgical treatment: Incidence, predictors, effect on survival, and impact of device selection.

BACKGROUND: Left ventricular assist devices (LVADs) are being used more frequently for treating refractory, advanced heart failure. However, infection remains a frequent complication. In this study, we analyzed the incidence of severe infections in LVAD recipients to determine its impact on survival. METHODS: From May 2009 through March 2016, 437 patients with advanced heart failure underwent implantation of a continuous-flow LVAD (n = 314, HeartMate II LVAD [Abbott Laboratories, Abbott Park, IL]; n = 123 HeartWare HVAD [Medtronic, Minneapolis, MN]). We analyzed the rate of severe device infection requiring surgical intervention or involving sepsis and the impact of severe infection on outcomes in patients on long-term LVAD support. RESULTS: Infection occurred in 244 patients (HeartMate II, n = 186; HVAD, n = 58); severe infections developed in 160 patients (HeartMate II, n = 119; HVAD, n = 41). HeartMate II recipients had 344 severe infection events (0.63 events per patient-year [EPPY]), whereas HeartWare recipients had 89 severe infection events (0.42 EPPY; P = 0.047). HeartMate II recipients had a higher incidence of pump infections (P < 0.001). Severe infections did not significantly affect survival (P = 0.42). CONCLUSIONS: Although HeartMate II patients had a significantly higher incidence of pump infections requiring surgical treatment, survival was not adversely affected. The difference in postoperative infection rates may be an important factor in device type selection.

A left ventricular end-diastolic dimension less than 6.0 cm is associated with mortality after implantation of an axial-flow pump.

OBJECTIVE: The effects of having a lower left ventricular end-diastolic dimension before HeartMate II (Thoratec Corp, Pleasanton, Calif) left ventricular assist device implantation remain unclear. We analyzed our single-center data on HeartMate II implantation to determine whether having a lower left ventricular end-diastolic dimension preoperatively was associated with inferior outcomes. METHODS: From November 2003 to March 2016, 393 patients with chronic heart failure underwent primary HeartMate II implantation. We compared the preoperative left ventricular end-diastolic dimension and associated survival outcomes of these patients to determine the left ventricular end-diastolic dimension cutoff for worse overall survival. Then, we compared the preoperative demographics, stroke rate, and mortality of patients with a left ventricular end-diastolic dimension above the cutoff for worse survival with those of patients with a left ventricular end-diastolic dimension below the cutoff. RESULTS: A Cox multivariate regression model showed that low left ventricular end-diastolic dimension was an independent predictor of mortality (hazard ratio, 1.49; P = .02). The Contal and O'Quigley method showed that overall survival postimplantation was decreased in patients with a left ventricular end-diastolic dimension less than 6.0 cm (n = 91). Kaplan-Meier analysis confirmed that the left ventricular end-diastolic dimension less than 6.0 cm group had lower overall survival than the left ventricular end-diastolic dimension 6.0 cm or greater group (P = .04). Furthermore, a competing-risk analysis showed that postoperative stroke was more common in the left ventricular end-diastolic dimension less than 6.0 cm group than in the left ventricular end-diastolic dimension 6.0 cm or greater group (P < .01). CONCLUSIONS: Overall survival was decreased and postoperative stroke was increased in HeartMate II recipients with a preoperative left ventricular end-diastolic dimension less than 6.0 cm. Future research should determine the left ventricular end-diastolic dimension cutoff values for safely implanting other support devices, and device designs should be improved to better accommodate the needs of patients with a limited left ventricle size.