The Hemodynamic Effects of Aortic Regurgitation in Patients Supported by a HeartMate 3 Left Ventricular Assist Device.

BACKGROUND: Aortic regurgitation (AR) is a common complication following left ventricular assist device (LVAD) implantation. We evaluated the hemodynamic implications of AR in patients with HeartMate 3 (HM3) LVAD at baseline and in response to speed changes. METHODS AND RESULTS: Clinically stable outpatients supported by HM3 who underwent a routine hemodynamic ramp test were retrospectively enrolled in this analysis. Patients were stratified based on the presence of at least mild AR at baseline speed. Hemodynamic and echocardiographic parameters were compared between the AR and non-AR groups. Sixty-two patients were identified. At the baseline LVAD speed, 29 patients (47%) had AR, while 33 patients (53%) did not. Patients with AR were older and supported on HM3 for a longer duration. At baseline speed, all hemodynamic parameters were similar between the groups including central venous pressure, pulmonary capillary wedge pressure, pulmonary arterial pressures, cardiac output and index, and pulmonary artery pulsatility index (p > 0.05 for all). During the subacute assessment, AR worsened in some, but not all, patients, with increases in LVAD speed. There were no significant differences in 1-year mortality or hospitalization rates between the groups, however, at 1-year, ≥ moderate AR and right ventricular failure (RVF) were detected in higher rates among the AR group compared to the non-AR group (45% vs. 0%; p < 0.01, and 75% vs. 36.8%; p = 0.02, respectively). CONCLUSIONS: In a cohort of stable outpatients supported with HM3 who underwent a routine hemodynamic ramp test, the presence of mild or greater AR did not impact the ability of HM3 LVADs to effectively unload the left ventricle during early subacute assessment. Although the presence of AR did not affect mortality and hospitalization rates, it resulted in higher rates of late hemodynamic-related events in the form of progressive AR and RVF.

A change of heart: Characteristics and outcomes of multiple cardiac retransplant recipients.

BACKGROUND: Among heart transplant (HT) recipients who develop advanced graft dysfunction, cardiac re-transplantation may be considered. A smaller subset of patients will experience failure of their second allograft and undergo repeat re-transplantation. Outcomes among these individuals are not well-described. METHODS: Adult and pediatric patients in the United Network for Organ Sharing (UNOS) registry who received HT between January 1, 1990 and December 31, 2020 were included. RESULTS: Between 1990 and 2020, 90 individuals received a third HT and three underwent a fourth HT. Recipients were younger than those undergoing primary HT (mean age 32 years). Third HT was associated with significantly higher unadjusted rates of 1-year mortality (18% for third HT vs. 13% for second HT vs. 9% for primary HT, p < .001) and 10-year mortality (59% for third HT vs. 42% for second HT vs. 37% for primary HT, p < .001). Mortality was highest amongst recipients aged >60 years and those re-transplanted for acute graft failure. Long-term rates of CAV, rejection, chronic dialysis, and hospitalization for infection were also higher. CONCLUSIONS: Third HT is associated with higher morbidity and mortality than primary HT. Further consensus is needed regarding appropriate organ stewardship for this unique subgroup.

Utility of a fusion protein T-cell co-stimulation blocker Belatacept in heart transplant recipients: Real world experience from a high volume center.

BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

The utilization of molecular microscope in management of heart transplant recipients in the era of noninvasive monitoring.

INTRODUCTION: Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. METHODS: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. CONCLUSIONS: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.

Combined heart and liver transplantation in a patient supported by left ventricular assist device (LVAD) with propionic acidemia.

Propionic acidemia (PA) is a rare inherited metabolic disease due to inborn errors of metabolism. PA results in the accumulation of abnormal organic acid metabolites in multiple systems, mainly the central nervous system and the heart. Cardiac complications include dilated cardiomyopathy (DCM) and carry a 40-50% increased mortality risk. Liver transplantation (LT) is required in PA patients when medical treatment fails and may prevent or slow down the cardiomyopathy progression. However, severe heart disease may be a serious contraindication to LT. We present a complicated case of a PA patient, supported with a Left Ventricular Assist Device, who underwent a heart and Liver transplant. PA patients are at increased risk for metabolic acidosis during surgery, with increased anion gap and hyperammonemia. A strict multi-disciplinary approach is needed to prevent and treat metabolic decompensation. The patient had a successful heart and liver transplant after a strict treatment protocol in the pre, intra, and post-operative periods. His case highlights the complexity of PA patients and the increased risk for metabolic decompensation during surgery and provides an insight into how to manage such complicated patients.

The role of temporary mechanical circulatory support as a bridge to advanced heart failure therapies or recovery.

PURPOSE OF REVIEW: Temporary mechanical circulatory support (tMCS) has become central in the treatment of refractory cardiogenic shock and can be used to bridge patients to durable MCS, heart transplant or recovery. This review will discuss contemporary data regarding bridging strategies utilizing tMCS. RECENT FINDINGS: There has been significant growth in tMCS use recently, driven by increased familiarity with tMCS devices, and increased experience with both implantation and management. Identifying goals of therapy at the time of therapy initiation can facilitate better outcomes. The three primary goals are bridge to recovery, bridge to heart transplantation or bridge to durable left ventricular assist device. Bridging to recovery requires adequate treatment of underlying conditions and optimization of haemodynamics. Bridging to heart transplantation has become more frequent following changes to the heart allocation policy. Despite early concerns, patients bridge with tMCS, including ventricular-arterial extracorporeal membrane oxygenation, do not appear to have worse posttransplant outcomes. When bridging to durable mechanical circulatory support, tMCS can be used to enhance end-organ dysfunction and improve perioperative outcomes. In situations in which none of these goals are attainable, palliative care plays a critical role to identify patient wishes and assist with withdrawal of care when necessary. SUMMARY: The use of tMCS, as a bridge to recovery or heart replacement therapy in patients with refractory cardiogenic shock has grown significantly over the past decade. Multiple device choices are available and must be chosen appropriately to address the specific situation and the goals of therapy.

The impact of diabetes mellitus on the clinical phenotype of hypertrophic cardiomyopathy.

AIMS: Diabetes mellitus (DM) aggravates the clinical features of ischaemic and hypertensive heart diseases and worsens the prognosis of heart failure patients. Hypertrophic cardiomyopathy (HCM) and diabetes coexist fairly frequently in elderly patients but the impact of DM on the clinical phenotype of HCM is yet unknown. We sought to describe if predominant features of heart failure in DM patients exist independently in HCM. METHODS AND RESULTS: We reviewed clinical characteristics of 937 patients, age ≥40, diagnosed with HCM, from two tertiary medical centres in Spain and Israel. A propensity score matched cohort of 294 patients was also analysed. Our cohort comprised 102 HCM patients with diabetes (8.7%). Patients with DM were older at diagnosis {median 56 [interquartile range (IQR) 47-67] vs. 53 (IQR 43-63), P = 0.02} and had a higher prevalence of comorbidities. Hypertrophic cardiomyopathy patients with DM had a higher prevalence of diastolic dysfunction, pulmonary hypertension, significant mitral regurgitation, and pacemaker implantation. Hypertrophic cardiomyopathy patients with DM had a higher New York Heart Association (NYHA) class (P < 0.001) and lower exercise capacity [7.0 METS (IQR 5.0-10.0) vs. 9.0 METS (IQR 6.6-11.0), P = 0.002]. These findings were independent of age, gender, country of origin, hypertension, and coronary artery disease. Patients with diabetes had a significantly higher 15-year mortality (22% vs. 15%, P = 0.03), with no differences in sudden cardiac death, appropriate implanted cardioverter-defibrillator therapy, or heart transplantation. CONCLUSION: Hypertrophic cardiomyopathy patients with diabetes are older and have a higher cardiovascular risk profile. They have a lower functional capacity and more heart failure symptoms due to diastolic dysfunction.

Structured, Protocol-Based Pulse-Oximetry Measurement Improves the Evaluation of Hypoxemic Patients at Hospital Admission.

BACKGROUND: Accurate pulse oximetry reading at hospital admission is of utmost importance, mainly for patients presenting with hypoxemia. Nevertheless, there is no accepted or evidence-based protocol for such structured measuring. OBJECTIVES: To devise and assess a structured protocol intended to increase the accuracy of pulse oximetry measurement at hospital admission. METHODS: The authors performed a prospective comparison of protocol-based pulse-oximetry measurement with non-protocol based readings in consecutive patients at hospital admission. They also calculated the relative percentage of improvement for each patient (before and after protocol implementation) as a fraction of the change in peripheral capillary oxygen saturation (SpO2) from 100%. RESULTS: A total of 460 patients were recruited during a 6 month period. Implementation of a structured measurement protocol significantly changed saturation values. The SpO2 values of 24.7% of all study participants increased after protocol implementation (ranging from 1% to 21% increase in SpO2 values). Among hypoxemic patients (initial SpO2 < 90%), protocol implementation had a greater impact on final SpO2 measurements, increasing their median SpO2 readings by 4% (3-8% interquartile range; P < 0.05). Among this study population, 50% of the cohort improved by 17% of their overall potential and 25% improved by 50% of their overall improvement potential. As for patients presenting with hypoxemia, the median improvement was 31% of their overall SpO2 potential. CONCLUSIONS: Structured, protocol based pulse-oximetry may improve measurement accuracy and reliability. The authors suggest that implementation of such protocols may improve the management of hypoxemic patients.

Reckless administration of QT interval-prolonging agents in elderly patients with drug-induced torsade de pointes.

A systematic review was conducted for all published case reports on drug-induced torsade de pointes (TdP) in elderly (≥80 years) patients to study if the administration of the offending agent was reckless. Overall, 61 reports on drug-induced TdP in patients aged 80-97 years were included in the analysis. Non-modifiable risk factors for drug-induced TdP (e.g. acute coronary syndrome, female gender and congestive heart failure), modifiable risk factors (e.g. hypokalemia, severe hypomagnesemia and digitalis toxicity) and reckless administration of a QT interval-prolonging agent (e.g. despite a known QT interval prolongation or a history of TdP, together with other QT interval prolonging agents in higher than recommended doses) were recorded in each case. Overall, 54 (88.5%) patients had non-modifiable risk factors for drug-induced TdP and 21 (34.4%) patients had modifiable risk factors. The administration of the offending agent was reckless in one half (n = 31; 50.8%) of the patients. The most prevalent reckless administration of a QT interval-prolonging agent was together with other QT interval-prolonging agents (n = 16; 51.6%) or despite QT interval prolongation (n = 8; 25.8%). In conclusion, although risk factors for drug-induced TdP are prevalent in elderly patients with drug-induced TdP, in approximately 50% of patients it appeared following a reckless administration of a QT interval-prolonging agent. In this population physicians should particularly avoid administration of two or more QT interval-prolonging agents simultaneously or administration of a QT interval-prolonging agent despite QT interval prolongation.

Low ALT blood levels are associated with lower baseline fitness amongst participants of a cardiac rehabilitation program.

BACKGROUND/OBJECTIVE: Objective assessment tools for patients' frailty are lacking. Such tools would have been highly valuable for assessment of candidates for cardiac rehabilitation programs. Low ALT (Alanine aminotransferase) values were recently shown to be a promising parameter for objective, quantitative frailly assessment. METHODS: This was a retrospective study of patients participating in a cardiac rehabilitation program. RESULTS: Patients with lower ALT activity levels at the initiation of rehabilitation program had lower estimated METs values (6.86 vs. 7.73; p < 0.001), shorter stress test duration (06:41 vs. 07:44 min; p < 0.001), higher resting heart rate (72 ± 13 vs. 70 ± 13 BPM; p = 0.01) and lower heart rate reserve (49 ± 24 vs. 54 ± 24; p < 0.001). Multivariate linear modeling demonstrated that ALT values were Independent determinants of baseline exercise capacity (expressed in METs). CONCLUSION: Lower ALT values, measured prior to the initiation of cardiac rehabilitation programs may indicate frailty of patients and be indicative for poor rehabilitation outcomes. Further, prospective studies should assess the potential correlation between ALT values and rehabilitation efficiency. We aimed to assess the potential correlation between the baseline ALT values and the baseline exercise capacity, as expressed in METs (Metabolic equivalent of tasks). 3806 patients were included in our study.

Crossed ectopic kidney: prenatal diagnosis and postnatal follow-up.

OBJECTIVE: The objective of this study is to investigate prenatal diagnosis and postnatal outcome of fetuses with crossed ectopic kidney. METHOD: Cases referred for an empty renal fossa and diagnosed with crossed ectopic kidney confirmed postnatally were analyzed retrospectively over a period of 10 years. Prenatal diagnosis was established following the detection of one kidney in a normal position and a second ipsilateral kidney fed by abnormal blood vessels on Doppler flow RESULTS: Between 2005 and 2015, 185 fetuses were referred for an empty renal fossa. Crossed ectopic kidney was diagnosed in 10 of them. Associated congenital urological anomalies included two cases of double collecting system and bilateral hydronephrosis in one. Associated extra renal findings were single umbilical artery (4/10), ventricular septal defects (1/10), and persistent left superior vena cava (1/10). On postnatal follow-up, bilateral vesicoureteral reflux was diagnosed in a case who presented prenatally with bilateral hydronephrosis and two cases of mild hydronephrosis. All cases were managed conservatively. CONCLUSION: Crossed ectopic kidney should be suspected in cases presenting with an empty renal fossa and a normal positioned kidney. Thorough anatomical scan should be performed as well as periodic follow-up throughout pregnancy. Postnatal nephrological follow-up is recommended. © 2017 John Wiley & Sons, Ltd.

The role of direct single monetary grants in residents' choice of field of residency.

BACKGROUND: In an attempt to address severe medical manpower shortages in several medical disciplines, the Israeli Ministry of Health offered grants to residents who chose one of these fields. METHODS: A total of 220 residents from various disciplines were surveyed on demographic, academic, and professional data, and asked to rank considerations in the choice of their field of residency. RESULTS: Residents in targeted fields attributed significantly more importance to the grant in their decision-making process (U = 3704.5, p < 0.001). This effect remained significant in a multivariate model (OR 1.67, 95%CI 1.32-2.10, p < 0.001). Higher age (OR 1.15, 95%CI 1.01-1.31, p = 0.031) and attribution of significance to the working conditions compared to other residency fields (OR 1.69, 95%CI 1.23-2.32, p = 0.001) were significantly associated with receptivity toward the grant in a multivariate analysis. DISCUSSION: Receptivity toward the offered grants correlated with real-life data shows a rise in physician in these fields, and the weak association between such receptivity and most variables tested may suggest that the grants were perceived as a property of the specific choice rather than a special bonus. CONCLUSIONS: Grants may be useful in diverting medical manpower. Further analysis and modeling are required to determine causal relationship and budgetary feasibility.

Pericarditis recurrence is associated with milder electrocardiographic, echocardiographic, and laboratory findings.

Recurrent pericarditis (RP) complicates approximately 30% of acute pericarditis (AP) cases. We sought to compare the prevalence and severity of objective findings seen in patients with RP. A retrospective single-center study during 2010-2019, including 765 patients diagnosed with AP. Clinical, electrocardiographic, echocardiographic, and laboratory findings were extracted from the local electronic health records. Recurrence during follow-up was documented in 134 patients (17.5%), with a median time to recurrence of 101 (± 59-251) days. The median age was 60 years (IQR 45-72), 68% were male. Most patients were defined as having idiopathic\viral pericarditis (64%). The clinical manifestation during the recurrent event of pericarditis was less prominent or attenuated when compared to the initial event-ECG signs (ST elevation 12% vs. 26%; p = 0.006, Knuckle sign 13% vs. 33%; p < 0.001, ST larger in lead L2 than L3 4% vs. 19%; p < 0.001), pericardial effusion moderate and above (11% vs. 30%; p = 0.02), and inflammatory markers (mean peak CRP levels 66 mg/l vs. 97 mg/l; p < 0.001). Similar results were seen in the subgroup of patients defined as having idiopathic\viral pericarditis. Up to 20% of patients who did not have ECG signs or a significant pericardial effusion in their 1st event demonstrated these findings during the recurrence, though still to a lesser extent compared with those who had these signs in their 1st event. The objective findings of AP are less pronounced during recurrent events. Future studies should focus on the role of advanced biomarkers and imaging in defining true RP events.

Artificial Intelligence Assessment of Biological Age From Transthoracic Echocardiography: Discrepancies with Chronologic Age Predict Significant Excess Mortality.

BACKGROUND: Age and sex can be estimated using artificial intelligence on the basis of various sources. The aims of this study were to test whether convolutional neural networks could be trained to estimate age and predict sex using standard transthoracic echocardiography and to evaluate the prognostic implications. METHODS: The algorithm was trained on 76,342 patients, validated in 22,825 patients, and tested in 20,960 patients. It was then externally validated using data from a different hospital (n = 556). Finally, a prospective cohort of handheld point-of-care ultrasound devices (n = 319; ClinicalTrials.gov identifier NCT05455541) was used to confirm the findings. A multivariate Cox regression model was used to investigate the association between age estimation and chronologic age with overall survival. RESULTS: The mean absolute error in age estimation was 4.9 years, with a Pearson correlation coefficient of 0.922. The probabilistic value of sex had an overall accuracy of 96.1% and an area under the curve of 0.993. External validation and prospective study cohorts yielded consistent results. Finally, survival analysis demonstrated that age prediction ≥5 years vs chronologic age was associated with an independent 34% increased risk for death during follow-up (P < .001). CONCLUSIONS: Applying artificial intelligence to standard transthoracic echocardiography allows the prediction of sex and the estimation of age. Machine-based estimation is an independent predictor of overall survival and, with further evaluation, can be used for risk stratification and estimation of biological age.

Hemodynamic Optimization by Invasive Ramp Test in Patients Supported With HeartMate 3 Left Ventricular Assist Device.

In patients supported by the HeartMate 3 left ventricular assist device (HM3 LVAD), pump speed adjustments may improve hemodynamics. We investigated the hemodynamic implications of speed adjustments in HM3 recipients undergoing hemodynamic ramp tests. Clinically stable HM3 recipients who underwent routine invasive hemodynamic ramp tests between 2015 and 2022 at our center were included. Filling pressure optimization, defined as central venous pressure (CVP) <12 mm Hg and pulmonary capillary wedge pressure (PCWP) <18 mm Hg, was assessed at baseline and final pump speeds. Patients with optimized pressures were compared to nonoptimized patients. Overall 60 HM3 recipients with a median age of 62 years (56, 71) and time from LVAD implantation of 187 days (124, 476) were included. Optimized filling pressures were found in 35 patients (58%) at baseline speed. Speed was adjusted in 84% of the nonoptimized patients. Consequently, 39 patients (65%) had optimized pressures at final speed. There were no significant differences in hemodynamic findings between baseline and final speeds (p > 0.05 for all). Six and 12 month readmission-free rates were higher in optimized compared with nonoptimized patients (p = 0.03 for both), predominantly due to lower cardiac readmission-free rates (p = 0.052). In stable outpatients supported with HM3 who underwent routine ramp tests, optimized hemodynamics were achieved in only 2 of 3 of the patients. Patients with optimized pressures had lower all-cause readmission rates, primarily driven by fewer cardiac-related hospitalizations.

Pumping for Two: Pregnancy in Patients Supported With a Left Ventricular Assist Device.

This review discusses the challenges and outcomes associated with pregnancy during left ventricular assist device (LVAD) support. Women account for a third of the heart failure population in the United States. Left ventricular assist devices have emerged as a safe and effective treatment option for patients with advanced heart failure. Pregnancy during LVAD support can occur, and it presents significant risks to both mother and fetus, including hemodynamic stress, thrombotic events, medication-associated teratogenicity, and uterine impingement. This literature review identified 10 cases of confirmed pregnancy during LVAD support, of which eight resulted in successful births. Maternal and fetal mortality occurred in one case, and there was a spontaneous abortion in one case. The review highlights the importance of a multidisciplinary approach, promotion of shared decision-making, thoughtful anticoagulation, adjustment of LVAD speed, and medication optimization to maintain hemodynamic support during pregnancy. Hemodynamic changes during pregnancy include increased cardiac output, heart rate, and plasma volume, as well as decreased systemic vascular resistance, which can impact LVAD support. Despite reduced pulsatility in LVAD-supported patients, ovulation and reproductive capacity might be preserved, and viable pregnancies may be achieved with appropriate management. The review provides insights into the risks and considerations for a viable pregnancy during LVAD support, including the need for ongoing research to inform joined decision-making.

The clinical course of patients with previous acute and recurrent pericarditis receiving the BNT162b2 vaccine.

Background: Vaccines against SARS-COV2 have been crucial in efforts against COVID19, yet there have been reports of pericarditis following vaccination with mRNA-based vaccines. Methods: We questioned consecutive patients with a history of acute pericarditis (AP) evaluated in the pericardial disease clinic during 3-11/2020 in a single tertiary center. Patients with significant myocardial involvement or pericarditis secondary to another systemic disease were excluded. Results: We included 64 patients in the final analysis. Mean age was 53.1 (±18), and 26 (41%) were female. At least 1 recurrence of AP was documented in 47 (73%) cases, 32 (50%) had ≥ 3 recurrences prior to vaccination. AP was considered to be idiopathic\viral in 45 (70%) cases, 20 (31%) cases were post-injury. All patients received at least 2 doses of the vaccine, and 48 patients (75%) received a 3rd dose. Two cases of breakthrough COVID19 infections were documented. Overall, 12 patients (19%) reported any adverse events. Of which, 2 had recurrent pericarditis. There was a trend for a younger age in those patients who had adverse events (median age 45 [IQR 36-61] vs. 60 [38-71], p = 0.08). no other significant difference was seen. Conclusion: In patients with a history of acute\recurrent pericarditis, the use of BNT162b2 was mostly uneventful, but some mild disease recurrences did occur.

Effect of levosimendan infusion prior to left ventricular assist device implantation on right ventricular failure.

OBJECTIVE: Investigate the safety and efficacy of preoperative levosimendan in patients undergoing left ventricular assist device (LVAD) implantation. METHODS: Consecutive patients who received LVADs (HeartMate-2, 3, HVAD) in a single tertiary medical center (2012-2018). INTERMACS profile 1 patients were excluded. The primary outcome was post-LVAD right ventricular failure (RVF) and inhospital mortality rates. The secondary outcomes included other clinical, echocardiographic and hemodynamic parameters at follow-up. RESULTS: Final cohort consisted of 62 patients (40[65%] in the levosimendan group and 22[35%] in the no-levosimendan group). Post-operative RVF rate and inotrope or ventilation support time were similar in the levosimendan and no-levosimendan groups (7.5% vs. 13.6%; P = 0.43, median of 51 vs. 72 h; P = 0.41 and 24 vs. 27 h; P = 0.19, respectively). Length of hospitalization, both total and in the intensive care unit, was not statistically significant (median days of 13 vs. 16; P = 0.34, and 3 vs. 4; P = 0.44, respectively). Post-operative laboratory and echocardiographic parameters and in-hospital complication rate did not differ between the groups, despite worse baseline clinical parameters in the Levosimendan group. There was no significant difference in the in-hospital and long term mortality rate (2.5% vs. 4.5%; P > 0.999 and 10% vs. 27.3% respectively; P = 0.64). CONCLUSIONS: Levosimendan infusion prior to LVAD implantation was safe and associated with comparable results without significant improved post-operative outcomes, including RVF.

Sex differences in patients undergoing heart transplantation and LVAD therapy.

INTRODUCTION: Left ventricular assist device (LVAD) and heart transplantation (HT) are the two life-sustaining therapies that have revolutionized the management of end-stage heart failure (HF). Yet, significant sex differences exist with respect to their use and effects. AREAS COVERED: This review summarizes sex differences in the utilization, outcomes, and complications of LVAD and HT. Particular emphasis is placed on leading clinical trials in the field, historical and recent large registries-based analyses, as well as contemporary technological and policy changes affecting these differences. EXPERT OPINION: Women with advanced HF remain under-treated with guideline-directed medical therapy and are less likely to be referred for consideration for LVAD and HT. This remains true despite newer LVAD technology and the new heart transplant allocation system. Community outreach, education, as well as increased representation of women in clinical research may reduce inequities.

Hypokinetic hypertrophic cardiomyopathy: clinical phenotype, genetics, and prognosis.

AIMS: To describe the phenotype, genetics, and events associated with the development of hypertrophic cardiomyopathy (HCM) with reduced ventricular function (HCMr). Heart failure in HCM is usually associated with preserved ejection fraction, yet some HCM patients develop impaired systolic function that is associated with worse outcomes. METHODS AND RESULTS: Our registry included 1328 HCM patients from two centres in Spain and Israel. Patients with normal baseline ventricular function were matched, and a competing-risk analysis was performed to find factors associated with HCMr development. Patient records were reviewed to recognize clinically significant events that occurred closely before the development of HCMr. Genetic data were collected in patients with HCMr. A composite of all-cause mortality or ventricular assist device (VAD)/heart transplantation was assessed according to ventricular function. Median age was 56, and 34% were female patients. HCMr at evaluation was seen in 37 (2.8%) patients, and 46 (3.5%) developed HCMr during median follow up of 9 years. HCMr was associated with younger age of diagnosis, poor functional class, and ventricular arrhythmia. Atrial fibrillation, pacemaker implantation, and baseline left ventricular ejection fraction (LVEF) of ≤55% were significant predictors of future HCMr development, while LV obstruction predicted a lower risk. Genetic testing performed in 53 HCMr patients, identifying one or more pathogenic variant in 38 (72%): most commonly in myosin binding protein C (n = 20). Six of these patients had an additional pathogenic variant in one of the sarcomere genes. Patients with baseline HCMr had a higher risk (hazard ratio 6.4, 4.1-10.1) for the composite outcome and for the individual components. Patients who developed HCMr in the course of the study had similar mortality but a higher rate of VAD/heart transplantation compared with HCM with normal LVEF. CONCLUSIONS: Hypertrophic cardiomyopathy with reduced ejection fraction is associated with heart failure and poor outcome. Arrhythmia, cardiac surgery, and device implantation were commonly documented prior to HCMr development, suggesting they may be either a trigger or the result of adverse remodelling. Future studies should focus on prediction and prevention of HCMr.