Circulation: Cardiovascular Interventions Editors’ Picks

Heart failure has become one of the fastest growing cardiovascular diagnoses, with estimates as high as 500 000 new cases per year.1,2 This growth is in part a result of the reductions in death from acute coronary syndromes, increased use of implantable cardioverter defibrillators, and improved survival with most cardiovascular interventions, which have led to this continued increase in the number of patients who develop progressive heart failure (HF). The estimated number of people in the United States with the diagnosis of HF may exceed 7 million, based on the estimated average prevalence of 2.6%,3,4 and a census of >300 million population (Figure 1).5,6 HF is clearly age related,1,–,4 with prevalence as low as 0.5% in those 65 years of age.2 This is an important demographic, because it is estimated that the number of people >65 years of age will double in the next 20 to 30 years.4,–,7 HF is not a homogeneous condition. Based primarily on data from recent hospital registries8,9 and other studies,10 nearly half of all patients have HF with preserved systolic function, and the other half have varying degrees of severity of HF with reduced systolic function. Although the prevalence of HF is higher in males at <70 years of age, overall HF is equally common in men and women. Unfortunately, the average survival of patients with either preserved or reduced systolic function is only 40% at 5 years after diagnosis,10,11 and may be as high as 80% when it reaches a refractory stage.12 One study of 3500 patients in Minnesota suggested that there is …

Cost-effectiveness analysis in cardiac surgery: A review of its concepts and methodologies

Serum albumin is an independent predictor of morbidity, including deep sternal wound infections, and mortality following cardiac surgery and left ventricular assist device (LVAD) implantation.1, 2 Preoperative hypoalbuminemia in patients being evaluated for LVAD implementation may be due to malnutrition and frailty, hepatic dysfunction due to both right and left heart failure, the cardiorenal syndrome, and systemic inflammation. Patients with hypoalbuminemia may potentially benefit from LVAD implantation since the combination of nutritional support and the reversal of heart failure may restore serum albumin to normal levels. On the other hand, the co-morbidities associated with hypoalbuminemia may increase perioperative morbidity and mortality and decrease long-term survival. Furthermore, patients with hypoalbuminemia undergoing LVAD implantation may not recover sufficiently to be considered candidates for heart transplantation. In view of the increasing costs associated with LVAD therapy,3 the known increased morbidity and mortality in patients with hypoalbuminemia, and the uncertainty of the option for heart transplantation, should patients with moderate and severe serum hypoalbuminemia undergo LVAD therapy? In this edition of the Journal, Critsinelis et al4 sought to determine short- and-long term survival in patients with low preoperative serum albumin levels who underwent continuous-flow LVAD implantation. In 526 patients who had undergone LVAD implantation at their center, 186 patients (35.4%) had moderate hypoalbuminemia (2.5-3.5 g/dL) and 18 (3.4%) had severe hypoalbuminemia (<2.5 g/dL). Patients with preoperative hypoalbuminemia were more likely to receive LVAD implementation for destination therapy, were more likely to have required preoperative circulatory support, had significantly lower preoperative hemoglobin levels and platelet counts, significantly higher white blood cell counts, and higher liver function enzyme levels. Hypoalbuminemia patients also had a higher incidence of postoperative morbidity, including infections and sepsis, gastrointestinal bleeding, neurological dysfunction, acute kidney injury, and an increased incidence of hospital readmissions. Preoperative hypoalbuminemia was also associated with significantly decreased early and long-term survival following LVAD implementation. However, hypoalbuminemia prior to LVAD implementation did not affect the success of bridge to transplantation and did not significantly affect survival after heart transplantation. Furthermore, there was no association between body mass index (BMI) and outcomes with LVAD implantation which suggests that the co-morbidities associated with hypoalbuminemia, and not preoperative BMI, are responsible for the increased morbidity and mortality associated with hypoalbuminemia. Patients with hypoalbuminemia, but with normal pre-albumin levels and a normal central venous pressure, had no difference in survival compared to patients with normal albumin levels. Should LVAD therapy be denied to patients with preoperative hypoalbuminemia? The answer lies in what co-morbidities responsible for preoperative hypoalbuminemia can be reversed following initiation of LVAD therapy. Reversing the sequelae of low cardiac output may improve appetite and absorption of nutrients, improve hepatic function, and reduce systemic inflammation. Critsinelis et al did not assess the effects of perioperative nutritional supplementation on perioperative morbidity and mortality in their patients. Furthermore, they limited their assessment to measuring only preoperative serum albumin levels. Hence, we do not know whether patients who had a significant increase in serum albumin levels post LVAD implantation had better short- and long-term survival. While deceased preoperative serum albumin levels are a marker for increased perioperative morbidity and decreased short- and long-term survival following LVAD implantation, the data from this study suggest that serum albumIn alone cannot be used to exclude patients for LVAD support who may be potential candidates for heart transplantation. These patients will require more aggressive perioperative nutritional supplementation and continued therapy for underlying co-morbidities in addition to LVAD support. Only then can we determine whether LVAD implementation can improve long- and short-time survival in patients with hypoalbuminemia.

The purpose of this study was to determine the effect of a combination of bone marrow mononuclear cell (BM-MNC) implantation and sarpogrelate, a selective 5-HT(2A) antagonist, on endothelial function in patients with critical limb ischemia (CLI). We evaluated the leg blood flow (LBF) responses to acetylcholine (ACh) and sodium nitroprusside before and after BM-MNC implantation in 16 patients with CLI. We divided patients with CLI into 2 groups: those cotreated with sarpogrelate orally for 12 weeks (sarpogrelate group, n = 8) and those who remained on conventional therapy (control group, n = 8). LBF was measured by strain gauge plethysmography. BM-MNC implantation improved ankle brachial pressure index, transcutaneous oxygen pressure, and pain-free walking time. There was no significant difference in these parameters between the 2 groups. Before BM-MNC implantation, LBF responses to ACh were similar in the sarpogrelate group and control group. Twelve weeks of BM-MNC implantation enhanced LBF responses to ACh in the sarpogrelate and control groups. After 12 weeks of BM-MNC implantation, LBF response to ACh was significantly greater in the sarpogrelate group than in the control group. BM-MNC implantation did not alter the LBF responses to sodium nitroprusside in either group. These findings suggest that BM-MNC implantation improved not only limb ischemic symptoms but also endothelium-dependent vasodilation in patients with CLI. A combination of BM-MNC implantation and sarpogrelate had a more beneficial effect on vascular function in these patients.

Systolic Nonclosure of the Mitral Valve: Two Left Ventricular Assist Device Patients with Pan-Cardiac Cycle Mitral Valve Opening During Shock States

Background— Bone-marrow mononuclear cell (BM-MNC) implantation improves ischemic symptoms in patients with critical limb ischemia (CLI). The purpose of this study was to evaluate long-term clinical outcomes after autologous BM-MNC implantation in patients with CLI. Methods and Results— We assessed long-term clinical outcomes after BM-MNC implantation in 51 patients with CLI, including 25 patients with peripheral arterial disease (PAD) and 26 patients with Buerger disease. Forty-six CLI patients who had no BM-MNC implantation served as control subjects. Median follow-up period was 4.8 years. The 4-year amputation-free rates after BM-MNC implantation were 48% in PAD patients and 95% in Buerger disease, and they were 0% in control PAD patients and 6% in control Buerger disease. The 4-year overall survival rates after BM-MNC implantation were 76% in PAD patients and 100% in Buerger disease, and they were 67% in control PAD patients and 100% in control Buerger disease. Multivariable Cox proportional hazards analysis revealed that BM-MNC implantation correlated with prevention of major amputation and that hemodialysis and diabetes mellitus correlated with major amputation. In Buerger disease, ankle brachial pressure index and transcutaneous oxygen pressure were significantly increased after 1 month and remained high during 3-year follow-up. However, in patients with PAD, ankle brachial pressure index and transcutaneous oxygen pressure significantly increased after 1 month and gradually decreased during 3-year follow-up and returned to baseline levels. Conclusions— These findings suggest that BM-MNC implantation is safe and effective in patients with CLI, especially in patients with Buerger disease. Clinical Trial Registration— URL: http://home.hiroshima-u.ac.jp/angio/ . Unique identifier: 001769.

Brief Report Cardiomems (CMEMS) have been demonstrated to reduce hospitalizations in symptomatic HF. The purpose of our study is to describe our experience of CMEMS in our 27 left ventricular assist device (LVAD) patients. We found that there was a 56% reduction in HF hospitalizations at 6 mo and up to 29% reduction in HF hospitalizations at 12 mo pre- and post-CMEMS placement. Further investigation is warranted in a large cohort with a particular focus on the effects on the hemocompatibility LVAD complications. Brief Communication Left ventricular assist devices are the standard of care for the treatment of patients with advanced heart failure (HF). Despite this therapy, nearly 20% of patients have residual HF symptoms resulting in increased morbidity, mortality, and decrease in quality of life. The CardioMEMS (CMEMS) pulmonary artery (PA) sensor allows for frequent collection of hemodynamic information and has been proven to reduce HF hospitalizations in chronic HF patients.1,2 Data regarding efficacy in the LVAD population is limited to small case series. We describe our single-center experience using the CMEMS system in this patient population. We performed a retrospective study of 27 LVAD patients who underwent placement of the CMEMS device between August 2018 and January 2020 at Ascension St. Vincent Data was extracted through the electronic medical record systems. Patients were selected based on high-risk features such as frequent hospitalizations pre CMEMS implant. Baseline characteristics and outcome analysis including HF hospitalizations occurring in the 1 y pre- and 6 mo and 1 y post-CMEMS implantation in these patients were collected. All implants were performed after LVAD placement without interruption of anticoagulation, with the majority (89%) performed by the right internal jugular approach without interruption of anticoagulation. Technique was similar among implanting cardiologists including gaining access with an 11 French Terumo sheath and either a 260 cm Cardiomems guidewire or 300 cm Steelcore to selectively engage the appropriately sized vessel in the left PA. A hand injection of a mixture of ~10 mL of iodinated contrast and normal saline was then used under fluoroscopy for vessel identification, followed by re-engagement of the vessel with the wire and the implant then performed as described by the IFU. At the time of implant, goal PADP was set for the patient, and subsequent PA pressure data was then used to adjust diuretics, guideline-directed medical therapy, or speed adjustments in a stepwise fashion at the discretion of the patient’s primary cardiologist or CMEMS implanter. Baseline demographics were collected and included a mean age of 56 with 71% male with all with end-stage HF with LVAD support with HM3 (55%), HM2 (9%), and HVAD (36%) with 43% as a bridge to transplant. There was no significant difference in pulmonary vascular resistance between LVAD recipients with and without CMEMS. As seen in Figure 1, there was a 58% reduction in HF hospitalizations at 6 mo and up to 29% reduction in HF hospitalizations at 12 mo pre- and post-CMEMS placement. When HF hospitalization was further delineated by primary or secondary diagnosis, this reduction was even more marked (64% at 6 mo and 47% at 1 y, respectively). The procedure was remarkably safe in this anticoagulated, continuous flow population, with only 3% of patients developing scant hemoptysis that resolved without any intervention.Figure 1.: Primary endpoint of HF hospitalizations.Major limitations to these observations exist including the limited number of patients examined in a retrospective and single-center nature. Additionally, patients were selected for PA sensor implant at the discretion of their primary cardiologist and influenced by factors such as adherence to treatment recommendations and monitoring, distance traveled to LVAD center and other clinical characteristics that may introduce significant bias. Hospitalizations remain a large burden for LVAD patients, with some reports of >70% of patients needing hospitalization within the first-year postimplant.3,4 Elevated filling pressures may not only lead to HF hospitalizations but also lead to hemocompatibility related adverse events that may further complications associated with LVADs contributing to morbidity5,6 further hospitalizations. If the signal of reduced hospitalization for HF as both a primary and secondary diagnosis can be replicated in a larger population, PA sensor monitoring may present a safe and unique opportunity to decrease morbidity in a population that often struggles with the adverse events associated with LVAD therapy. Further investigation is required to examine the generalizability of these findings and whether other adverse events such as right ventricular failure, hemocompatibility related adverse events, or infection are truly impacted by more intensive hemodynamics monitoring.

Our goal was to provide a picture of left ventricular assist device (LVAD) activity in France between 2007 and 2016 based on the multicentric ASSIST-ICD registry. We retrospectively collected 136 variables including in-hospital data, follow-up survival rates and adverse events from 671 LVAD recipients at 20 out of 24 LVAD implant centres in France. The average follow-up time was 1.2 years (standard deviation: 1.4); the total follow-up time was 807.5 patient-years. The included devices were the HeartMate II®, HeartWare LVAS® or Jarvik 2000®. The overall likelihood of being alive while on LVAD support or having a transplant (primary end point) at 1, 2, 3 and 5 years postimplantation was 65.2%, 59.7%, 55.9% and 47.7%, respectively, given a cumulative incidence of 29.2% of receiving a transplant at year 5. At implantation, 21.5% of patients were on extracorporeal life support. The overall rate of cardiogenic shock at implantation was 53%. The major complications were driveline infection (26.1%), pump pocket or cannula infection (12.6%), LVAD thrombosis (12.2%), ischaemic (12.8%) or haemorrhagic stroke (5.4%; all strokes 18.2%), non-cerebral haemorrhage (9.1%) and LVAD exchange (5.2%). The primary end point (survival) was stratified by age at surgery and by the type of device used, with inference from baseline profiles. The primary end point combined with an absence of complications (secondary end point) was also stratified by device type. The ASSIST-ICD registry provides a real-life picture of LVAD use in 20 of the 24 implant centres in France. Despite older average age and a higher proportion of patients chosen for destination therapy, survival rates improved compared to those in previous national registry results. This LVAD registry contrasts with other international registries because patients with implants have more severe disease, and the national policy for graft attribution is distinct. We recommend referring patients for LVAD earlier and suggest a discussion of the optimal timing of a transplant for bridged patients (more dismal results after the second year of support?).

The objective of this autopsy study was to determine whether gastrointestinal angiodysplasia develops during continuous-flow left ventricular assist device (LVAD) support. LVAD support causes pathologic degradation of von Willebrand factor (vWF) and bleeding from gastrointestinal angiodysplasia at an alarming rate. It has been speculated that LVAD support itself may cause angiodysplasia. The relationship to abnormal vWF metabolism is unknown. We tested the hypothesis that abnormal gastrointestinal vascularity develops during continuous-flow LVAD support. Small bowel was obtained from deceased humans, cows, and sheep supported with a continuous-flow LVAD (n=9 LVAD, n=11 control). Transmural sections of jejunum were stained with fluorescein isothiocyanate-conjugated isolectin-B4 for endothelium to demarcate vascular structures and quantify intestinal vascularity. Paired plasma samples were obtained from humans before LVAD implantation and during LVAD support (n=41). vWF multimers and degradation fragments were quantified with agarose and polyacrylamide gel electrophoresis and immunoblotting. Abnormal vascular architecture was observed in the submucosa of the jejunum of human patients, cows, and sheep supported with a continuous-flow LVAD. Intestinal vascularity was significantly higher after LVAD support versus controls (5.2±1.0% versus 2.1±0.4%, P=0.004). LVAD support caused significant degradation of high-molecular-weight vWF multimers (-9±1%, P<0.0001) and accumulation of low-molecular-weight vWF multimers (+40±5%, P<0.0001) and vWF degradation fragments (+53±6%, P<0.0001). Abnormal intestinal vascular architecture and LVAD-associated vWF degradation were consistent findings in multiple species supported with a continuous-flow LVAD. These are the first direct evidence that LVAD support causes gastrointestinal angiodysplasia. Pathologic vWF metabolism may be a mechanistic link between LVAD support, abnormal angiogenesis, gastrointestinal angiodysplasia, and bleeding.

Aortic regurgitation during continuous-flow left ventricular assist device support: An insufficient understanding of an insufficient lesion

Advanced heart failure is a chronic, systemic disease, which affects other organs in ways that are incompletely understood. Patients with advanced heart failure commonly develop congestive hepatopathy, which may lead to progressive hepatic injury and fibrosis. Because the independent adverse effects of hepatic dysfunction on early and late outcomes after continuous flow left ventricular assist devices have also not been entirely demonstrated, we review its impact on this patient population. Although early mortality is increased in patients with significantly elevated total bilirubin before implant, early improvement in hepatic function is consistently observed following left ventricular assist device (LVAD) implantation, and this early improvement remains stable during late follow-up. Furthermore, a growing experience with expanded application of LVAD therapy in special patient populations, such as those with restrictive cardiomyopathy or congenital heart disease, demonstrates improved outcomes with LVAD compared with continued medical therapy. Although these outcomes are encouraging in the context of hepatic dysfunction not being considered a precluding factor in isolation, careful patient selection and preoperative optimization should be employed to ensure acceptable risk and a durable outcome. Significant preoperative hepatic dysfunction can increase early mortality in patients undergoing LVAD implant, but long-term outcomes in early survivors demonstrate improvement in measures of hepatic function, which is maintained during follow-up. Numerous perioperative considerations are imperative to optimize to ensure a durable outcome with LVAD in these patients.

Pulmonary Artery Wedge Pressure Respiratory Variation Predicts Hemodynamic Improvement with Increased LVAD Speed

Is Glycosylated Hemoglobin a Reliable Marker of Diabetes Management in Advanced Heart Failure Patients on Durable Mechanical Circulatory Support?

Changes in Sarcomeric and Non-sarcomeric Cytoskeletal Proteins and Focal Adhesion Molecules During Clinical Myocardial Recovery After Left Ventricular Assist Device Support

In June the National Institute for Health and Clinical Excellence (NICE) published welcome but bewildering guidelines for short term circulatory support with left ventricular assist devices (LVADs) as a bridge...