Depression and Anxiety in Heart Transplant Recipients: Prevalence and Impact on Post-Transplant Outcomes.

BACKGROUND: Depression and anxiety (DA) are common mental disorders in patients with chronic diseases, but the research regarding their prevalence in heart transplantation (HTx) is still limited. METHODS: We performed an analysis of the prevalence and prognostic relevance of DA in patients who underwent HTx between 2010 and 2018 in Germany. Data were obtained from Allgemeine Ortskrankenkasse (AOK), which is the largest public health insurance provider. RESULTS: Overall, 694 patients were identified. More than a third of them were diagnosed with DA before undergoing HTx (n = 260, 37.5%). Patients with DA more often had an ischaemic cardiomyopathy (p < 0.001) and a history of previous myocardial infarction (p = 0.001) or stroke (p = 0.002). The prevalence of hypertension (p < 0.001), diabetes (p = 0.004), dyslipidaemia (p < 0.001) and chronic kidney disease (p = 0.003) was higher amongst transplant recipients with DA. Patients with DA were more likely to suffer an ischaemic stroke (p < 0.001) or haemorrhagic stroke (p = 0.032), or develop septicaemia (p = 0.050) during hospitalisation for HTx. Our analysis found no significant differences between the groups with respect to in-hospital mortality. The female sex and mechanical circulatory support were associated with an inferior prognosis. Pretransplant non-ischaemic cardiomyopathy was related to a favourable outcome. CONCLUSIONS: DA affect up to a third of the population undergoing HTx, with a greater prevalence in patients with comorbidities. DA are associated with a higher incidence of stroke and septicaemia after HTx.

Effects of Angiotensin Receptor-Neprilysin Inhibitors (ARNIs) on the Glucose and Fat Metabolism Biomarkers Leptin and Fructosamine.

(1) Background: Heart failure with reduced ejection fraction (HFrEF) remains a major health burden. Angiotensin-Receptor-Neprilysin-Inhibitors (ARNIs) are an established HFrEF therapy which increases natriuretic peptide levels by inhibiting neprilysin. Leptin is a lipid metabolism parameter, which is also involved in glucose metabolism and is suggested to correlate with HF burden. While the hormone also seems to interact with neprilysin, potential associations with ARNI therapy have not been investigated yet. (2) Methods: To study this issue, we measured levels of leptin and fructosamine in consecutive 72 HFrEF patients before initiation of ARNI therapy and 3-6 months after initiation of therapy in two European centers. Biomarker levels were correlated with clinical parameters including ejection fraction, LVEF, and NYHA class. (3) Results: During a follow-up of up to 6 months, clinical parameters improved significantly (LVEF: 30.2 ± 7.8% to 37.6 ± 10.0%, (p < 0.001) and a significant improvement of the mean NYHA class with initial 32 patients in NYHA III or IV and 8 patients in NYHA class III/IV during the follow up (p < 0.001). The initial NT-proBNP levels of 2251.5 ± 2566.8 pg/mL significantly improved to 1416.7 ± 2145 pg/mL, p = 0.008) during follow up. ARNI therapy was also associated with an increase in leptin levels (17.5 ± 23.4 µg/L to 22.9 ± 29.3, p < 0.001) and furthermore, affected glucose metabolism indicated by elevation of fructosamine values (333.9 ± 156.8 µmol/L to 454.8 ± 197.8 µmol/L, p = 0.013). (4) Conclusion: while in the early phase of therapy, ARNI promotes clinical improvement of HFrEF, and it also seems to affect fat and glucose parameters, indicating significant metabolic implications of this therapy regime.

To hit a home run as a heterotopic heart recipient-living with two hearts for over three decades: a case report.

Heterotopic heart transplantation (HHT) is an alternative to the orthotopic technique in selected patients with terminal heart failure. We report the case of the longest survival after HHT, with an uneventful follow-up for over three decades after transplantation. At the age of 25 years, endomyocardial fibrosis following myocarditis rendered the patient's native heart unable to maintain the body's needs. An allograft provided a second chance at life. The HHT technique was favoured due to severe pulmonary hypertension. The patient had an uneventful follow-up since then. The scarcity of donors and the revolutionary advances in the mechanical circulatory device field restricted the utilization of the HHT technique, but it has the potential to provide an excellent prognosis with a good quality of life.

Diltiazem as a cyclosporine A-sparing agent in heart transplantation: Benefits beyond dose reduction.

Diltiazem (DZ) is widely prescribed in transplant recipients because of its drug-drug interactions with calcineurin inhibitors (CNI). However, these interactions have been primarily investigated in renal transplantation, and data regarding the long-term efficacy and safety of DZ in orthotopic heart transplantation (OHT) are still sparse. Our study aimed to elucidate the extent to which the co-prescription of DZ reduces the dose required to maintain adequate blood levels of cyclosporine A (CsA) and the resulting effect on morbidity and mortality in OHT recipients. We performed a retrospective single-center analysis of OHT recipients on a long-term immunosuppressive regimen based on CsA and mycophenolate mofetil (MMF). The study population consisted of 95 adult OHT recipients with a mean follow-up of 15.8 ±â€…6.7 years. DZ was co-prescribed in 39 subjects (41.1%) and was associated with a 28.6% reduction of the mean CsA daily dose (P < .001). Patients on DZ had less frequent rejection episodes (P = .002), better renal function (P = .009) and a lower rate of end-stage renal disease (P = .008). Additionally, they developed later cardiac allograft vasculopathy (CAV). We observed no prognostic relevance of DZ co-prescription in univariate and multivariate Cox-regression analyses. In addition to reducing the CsA dose required to maintain adequate blood through levels, DZ may have nephroprotective properties in OHT. The co-administration of DZ may decelerate the development of CAV and reduce the frequency of the rejection episodes. However, the beneficial influence on morbidity has no impact on mortality.

Permanent pacing in a very long-term follow-up after orthotopic heart transplantation: A matter of when or why?

BACKGROUND: Orthotopic heart transplantation (OHT) is associated with a high incidence of conduction disturbances (CD) leading to permanent pacemaker (PPM) implantation. However, the improved posttransplant survival raises the question about the pacemaker dependence (PD) in a prolonged follow-up. HYPOTHESIS: The prevalence of PPM in OHT is high but not all patients are PD in a very long-term follow-up. Device implantation has no prognostic relevance. METHODS: We performed a retrospective analysis of patient medical records focusing on device interrogation data at the most recent follow-up. RESULTS: The study population consisted of 183 patients with a mean follow-up of 15.0 ± 6.8 years. One-fourth of the patients had undergone PPM implantation (n = 49, 26.8%). Among these, two-thirds were PD at last follow-up (n = 32, 65.3%). PPM was more often in biatrial OHT and cardiac allograft vasculopathy (OR 3.0, 95% CI 1.26-7.29, p = .013 and OR 2.0, 95% CI 1.03-3.87, p = .041, respectively). Early sinus node dysfunction (SND) was the most persistent CD. PPM was associated with a poorer outcome in OHT (HR 1.9, 95% CI 1.06-3.46, p = .031) and a higher rate of fatal septicemia (HR 5.1, 95% CI 1.41-18.14, p = .013). CONCLUSIONS: One-fourth of the OHT recipients develop CD requiring PPM implantation, although one-third among these are not PD in follow-up. Early SND is associated with a higher rate of PD. PPM is associated with an inferior prognosis.

Cardiac allograft vasculopathy in a long-term follow-up after heart transplantation: Role of remnant cholesterol in residual inflammation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major prognosis limiting factor in heart transplantation (HTx). Disease development and progression are influenced by multiple determinants, but the role of remnant cholesterol (RC) in CAV has not yet been investigated. Therefore, the present study aimed to assess the prevalence of CAV in a very long-term follow-up after orthotopic HTx and to examine the role of RC in residual inflammation despite secondary prevention. METHODS: Herein, is a retrospective analysis of patient data collected at the last follow-up visit in an outpatient setting. Additionally, RC levels were calculated based upon cholesterol profile. RESULTS: The study population consisted of 184 patients with a mean follow-up of 15.0 ± 6.8 years. More than 40% of the overall cohort had CAV at last follow-up. The mean RC was 27.1 ± 14.7 mg/dL. Patients with CAV had significantly elevated RC despite intensified statin treatment (p = 0.018). A positive correlation was observed between RC and interleukin-6 as a marker of residual inflammation. Elevated RC and prolonged follow-up emerged as significant factors related to CAV in a multivariate analysis (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.5-5.5, p = 0.001 and OR 3.3, 95% CI 1.4-7.7, p = 0.006, respectively), whereas mycophenolate mofetil was inversely associated with CAV (OR 0.4, 95% CI 0.2-0.9, p = 0.034). CONCLUSIONS: Remnant cholesterol has proinflammatory properties and is associated with CAV development in HTx. Thus, RC should be concerned as an additional tool for risk assessment.

Sustained Impairment in Cardiopulmonary Exercise Capacity Testing in Patients after COVID-19: A Single Center Experience.

Background: Following COVID-19, patients often present with ongoing symptoms comparable to chronic fatigue and subjective deterioration of exercise capacity (EC), which has been recently described as postacute COVID-19 syndrome. Objective: To objectify the reduced EC after COVID-19 and to evaluate for pathologic limitations. Methods: Thirty patients with subjective limitation of EC performed cardiopulmonary exercise testing (CPET). If objectively limited in EC or deteriorated in oxygen pulse, we offered cardiac stress magnetic resonance imaging (MRI) and a follow-up CPET. Results: Eighteen male and 12 female patients were included. Limited relative EC was detected in 11/30 (36.7%) patients. Limitation correlated with reduced body weight-indexed peak oxygen (O2) uptake (peakV̇O2/kg) (mean 74.7 (±7.1) % vs. 103.6 (±14.9) %, p < 0.001). Reduced peakV̇O2/kg was found in 18/30 (60.0%) patients with limited EC. Patients with reduced EC widely presented an impaired maximum O2 pulse (75.7% (±5.6) vs. 106.8% (±13.9), p < 0.001). Abnormal gas exchange was absent in all limited EC patients. Moreover, no patient showed signs of reduced pulmonary perfusion. Using cardiac MRI, diminished biventricular ejection fraction was ruled out in 16 patients as a possible cause for reduced O2 pulse. Despite noncontrolled training exercises, follow-up CPET did not reveal any exercise improvements. Conclusions: Deterioration of EC was not associated with ventilatory or pulmonary vascular limitation. Exercise limitation was related to both reduced O2 pulse and peakV̇O2/kg, which, however, did not correlate with the initial severity of COVID-19. We hypothesize that impaired microcirculation or limited peripheral O2 utilization might be causative for prolonged deterioration of EC following acute COVID-19 infection.

Minimally Invasive Implantation of HeartWare Assist Device and Simultaneous Tricuspid Valve Reconstruction Through Partial Upper Sternotomy.

Left ventricular assist device (LVAD) implantation is a well-established therapy to support patients with end-stage heart failure. However, the operative procedure is associated with severe trauma. Third generation LVADs like the HeartWare assist device (HeartWare, Inc., Framingham, MA, USA) are characterized by enhanced technology despite smaller size. These devices offer new minimally invasive surgical options. Tricuspid regurgitation requiring valve repair is frequent in patients with the need for mechanical circulatory support as it is strongly associated with ischemic and nonischemic cardiomyopathy. We report on HeartWare LVAD implantation and simultaneous tricuspid valve reconstruction through minimally invasive access by partial upper sternotomy to the fifth left intercostal space. Four male patients (mean age 51.72 ± 11.95 years) suffering from chronic heart failure due to dilative (three patients) and ischemic (one patient) cardiomyopathy and also exhibiting concomitant tricuspid valve insufficiency due to annular dilation underwent VAD implantation and tricuspid valve annuloplasty. Extracorporeal circulation was established via the ascending aorta, superior vena cava, and right atrium. In all four cases the LVAD implantation and tricuspid valve repair via partial median sternotomy was successful. During the operative procedure, no conversion to full sternotomy was necessary. One patient needed postoperative re-exploration because of pericardial effusion. No postoperative focal neurologic injury was observed. New generation VADs are advantageous because of the possibility of minimally invasive implantation procedure which can therefore minimize surgical trauma. Concomitant tricuspid valve reconstruction can also be performed simultaneously through partial upper sternotomy. Nevertheless, minimally invasive LVAD implantation is a challenging operative technique.

Mechanical circulatory support for patients with peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) challenges different disciplines including gynecologists, cardiologists and cardiac surgeons. It is a severe cardiac failure occurring at the end of pregnancy or within the first months after delivery. Urgent intervention is necessary to stabilize hemodynamics with appropriate medication and mechanical assist support. Data of 4 patients with PPCM at a mean age of 28.2 years were analyzed retrospectively. Echocardiography was used to evaluate cardiac function. Despite varying courses of PPCM all women received left ventricular assist devices (LVAD) since their hemodynamics could not be stabilized by medical treatment. Mean gestational week at delivery was 31.5 ± 4.9. Left ventricular ejection fractions of all patients were severely impaired (17.8 ± 3.5 %) before LVAD implantations. After long-term mechanical support (282 and 417 days, respectively) 2 patients were successfully transplanted. Two other females could be weaned from LVAD therapy after 944 and 612 days, respectively. LVAD explanations were performed according to a standardized weaning protocol. Myocardial recovery was confirmed by regular echocardiography, spiroergometry and right heart catheterization. Mechanical assist device support is a surgical strategy either as bridge to transplantation or as bridge to recovery for patients with PPCM.

Implantation of left ventricular assist devices under extracorporeal life support in patients with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a rare but life-threatening side effect of heparin therapy. It is a demanding therapeutic challenge in patients undergoing left ventricular assist device (LVAD) implantation. We present our experience with LVAD implantation under extracorporeal life support (ECLS) in patients suffering from HIT. Seven patients (mean age 54.0 ± 16.7 years, 1 female, 6 male patients) suffering from acute heart failure were stabilized with ECLS. Under heparin therapy, they all showed a sudden decrease of mean platelet count (maximum 212.6 ± 41.5 tsd/µl; minimum 30.7 ± 13.1 tsd/µl). Due to the clinical suspicion of HIT anticoagulation was switched from heparin to argatroban (aPTT 70-80 s.). No improvement of cardiac function could be detected under ECLS, so LVAD implantation was indicated. We performed LVAD implantation under ECLS. During LVAD implantation under argatroban (aPTT of 50-60 s.) one patient developed massive intraventricular thrombus formations, so the device had to be removed. In 6 cases, we could successfully perform LVAD implantation under argatroban with a higher aPTT of 70-80 s and modified operative strategy. Four patients needed postoperative re-exploration because of bleeding complications. Perioperative management of LVAD patients under argatroban anticoagulation is very difficult. We were able to minimize the perioperative risk for thrombosis with a target aPTT of 70-80 s. To keep the phase of stasis within the device as short as possible we anastomosed the VAD outflow graft to the ascending aorta first before connecting the device to the apex. However, postoperative bleeding complications are frequent.

Implanting a Nonpulsatile Axial Flow Left Ventricular Assist Device as a Bridge to Transplant for Systemic Ventricular Failure After A Mustard Procedure.

Right (systemic) ventricular failure is well described after a Mustard procedure for transposition of the great arteries. Sixty-one percent of patients have been reported to show moderate-to-severe dysfunction of the systemic ventricle, 25 years after repair of transposition of the great arteries by a Mustard procedure. In such cases, heart transplant often seems to be the only option. When severe heart failure with hemodynamic instability develops, the only way to bridge these patients to a transplant is implantation of a mechanical circulatory support system. Because of the special anatomic features of the right ventricle, the implantation procedure can be challenging. Here, we report the case of a patient who underwent a left ventricular assist device implant owing to severe heart failure, 36 years after undergoing a Mustard procedure.

Prospective study of everolimus with calcineurin inhibitor-free immunosuppression in maintenance heart transplant patients: results at 2 years.

BACKGROUND: Few studies have examined everolimus therapy with calcineurin inhibitor (CNI) withdrawal in maintenance heart transplant patients. METHODS: In a prospective, single-arm, single-center study, CNI-treated heart transplant patients were converted to everolimus and were followed up for 24 months. The primary endpoints were kidney function and arterial hypertension at 12 and 24 months after conversion. RESULTS: Fifty-eight patients were recruited (mean time posttransplant 5.6±3.7 years), 55 of whom (91.7%) had renal impairment. Mean creatinine clearance increased from 43.6±21.1 mL/min to 49.5±21.2 mL/min at month 24 (P=0.02). Median blood pressure increased from 120/80 mm Hg at baseline to 122.5/80 mm Hg (P=0.008 and 0.006 for systolic and diastolic pressure, respectively). Lipid parameters did not change significantly over the 24-month follow-up. Early resolution of most non-renal CNI-related adverse events was sustained. CNI therapy was re-introduced at a mean of 309 days (range, 31-684 days) in eight patients after month 6 due to adverse events (n=13) or withdrawal of consent (n=2). No significant changes in cardiac function parameters were observed. CONCLUSIONS: CNI-free immunosuppression with everolimus is an effective and safe option in selected heart transplant maintenance patients. Most adverse effects under everolimus occurred early after conversion and generally resolved without intervention within a few weeks. Refining selection criteria may reduce the need to re-introduce CNI therapy.

Pre-operative prediction of post-VAD implant mortality using easily accessible clinical parameters.

BACKGROUND: Mortality rates are high after implantation of a ventricular assist device (VAD), occurring mainly in the early phase post-implant during the time in the intensive care unit (ICU). Pre-operative selection criteria, which predict successful outcome, are difficult to evaluate. We implemented a pre-operative risk score to predict mortality in the ICU after VAD implantation by using easily obtained and quickly accessible clinical parameters. METHODS: In 241 VAD patients, 100 pre-operative markers were related to mortality in the ICU using univariate analysis and ROC curves, followed by multinomial logistic regression analyses. RESULTS: The mortality rate in the ICU was 32.0%. Univariate statistical analysis revealed 34 parameters that were significantly associated with mortality in the ICU. Of these, multinomial logistic regression identified 13 markers as significant risk factors. These included demographic data (age >50 years); clinically/procedurally relevant data (ischemic cardiomyopathy [ICM], re-do surgery, on extracorporeal membrane oxygenation [ECMO], on intra-aortic balloon pump [IABP], previous cardiac surgery, ventilation, emergency implant, inotropic support, renal replacement therapy, pre-operative resuscitation, transfusion) and laboratory values (blood urea nitrogen [BUN] >40 mg/dl, creatinine >1.5 mg/dl, lactate >3 mg/dl, platelets <100 x 10(3)/microl, white blood cell [WBC] count >13 x 10(3)/microl, C-reactive protein [CRP] >8 mg/dl, hemoglobin <12 g/dl, hematocrit <35%, lactate dehydrogenase [LDH] >500 U/liter, creatine kinase [CK] >200 U/liter, troponin >20 ng/ml). A weighted risk score was implemented with a maximum of 50 points. The risk for mortality in the ICU was as follows: low (15.8%), <15 points; medium (48.2%), 16 to 30 points; and high (65.2%), >30 points. CONCLUSIONS: Easily obtained and quickly accessible clinical parameters can inform potential patients, relatives, and physicians pre-operatively about the risk of death in the ICU after VAD implantation.

Risk stratification in chronic heart failure: independent and incremental prognostic value of echocardiography and brain natriuretic peptide and its N-terminal fragment.

BACKGROUND: It was the aim of this study to compare the prognostic impact of echocardiography and brain natriuretic peptide and its N-terminal fragment (NT-proBNP) in patients with chronic heart failure (CHF). METHODS: In all, 73 patients with CHF underwent conventional 2-dimensional/Doppler echocardiography and Doppler tissue analysis of systolic, early and late diastolic mitral annular velocities. The mitral filling pattern was classified as restrictive or nonrestrictive. NT-proBNP measurements were carried out on a bench-top analyzer. A cardiac event (rehospitalization caused by worsening CHF, cardiac death, urgent cardiac transplantation) was defined as combined study end point. RESULTS: During follow-up of 226 +/- 169 days, 27 patients had an event (rehospitalization because of CHF, n = 18; cardiac death, n = 7; urgent transplantation, n = 2). On multivariate Cox regression analysis, a restrictive filling pattern, NT-proBNP, the ratio of peak early diastolic mitral flow to mitral annular E' velocity were independent prognostic predictors. A risk stratification model based on the 3 strongest independent predictors separated groups into those with good, intermediate, and poor outcome (event-free survival of 78%, 46%, and 0%, respectively). CONCLUSIONS: In patients with CHF, Doppler echocardiography, Doppler tissue imaging, and NT-proBNP provide independent and incremental prognostic information. A combined use of echocardiography and NT-proBNP may help to improve risk stratification in this patient population.