Cardiotoxicity of Iron and Zinc and Their Association with the Mitochondrial Unfolded Protein Response in Humans.

This study was designed to examine the association between myocardial concentrations of the trace elements Cu, Fe, Mn, Mo, and Zn and the expression of mitochondrial unfolded protein response (UPRmt) elements and the age of patients who received heart transplantation or a left-ventricular assist device (ageHTx/LVAD). Inductively coupled plasma mass spectrometry was used to determine the concentration of Cu, Fe, Mn, Mo, and Zn in the myocardium of control subjects and patients undergoing heart transplantation or left-ventricular assist device (LVAD) implantation. We used ELISA to quantify the expression of UPRmt proteins and 4-Hydroxynonenal (4-HNE), which served as a marker of oxidative-stress-induced lipid peroxidation. Concentrations of Cu, Mn, Mo, and Zn were similar in the control and heart failure (HF) myocardium, while Fe showed a significant decrease in the HF group compared to the control. A higher cumulative concentration of Fe and Zn in the myocardium was associated with reduced ageHTx/LVAD, which was not observed for other combinations of trace elements or their individual effects. The trace elements Cu, Mn, and Zn showed positive correlations with several UPRmt proteins, while Fe had a negative correlation with UPRmt effector protease YME1L. None of the trace elements correlated with 4-HNE in the myocardium. The concentrations of the trace elements Mn and Zn were significantly higher in the myocardium of patients with dilated cardiomyopathy than in patients with ischemic cardiomyopathy. A higher cumulative concentration of Fe and Zn in the myocardium was associated with a younger age at which patients received heart transplantation or LVAD, potentially suggesting an acceleration of HF. A positive correlation between myocardial Cu, Mn, and Zn and the expression of UPRmt proteins and a negative correlation between myocardial Fe and YME1L expression suggest that these trace elements exerted their actions on the human heart by interacting with the UPRmt. An altered generation of oxidative stress was not an underlying mechanism of the observed changes.

Enterobacter cloacae septicemia in a triple-cannula extracorporeal membrane oxygenation circulatory support treated with Seraph-100 Microbind affinity blood filter.

Bloodstream infections (BSI) are frequently encountered during extracorporeal membrane oxygenation (ECMO) support. Once septicemia is observed, treatment should be rapid, adequate, and multifaceted, particularly in advanced ECMO configurations. We report on a case of a 60-year-old male patient with acute-on-chronic heart failure due to ischemic cardiomyopathy. The treatment was complicated by cardiogenic shock requiring veno-arterial ECMO support, and, due to persistent pulmonary congestion, an upgrade with an additional left-atrial drainage cannula. After seven days of ECMO support, septicemia with shock ensued. Ex iuvantibus antibiotic treatment was started promptly. We wanted to minimize the likelihood of bacterial biofilm build-up requiring an exchange of the ECMO circuit and cannula, which was expected to be challenging. Therefore, we added a Seraph-100 Microbind affinity blood filter (providing blood purification with the potential for rapid bacterial clearance) to the ECMO circuit. Initial blood cultures tested positive for Enterobacter cloacae. Following a course of Seraph-100 treatment, bacteremia, septicemia, and shock resolved. There was no need for a circuit or cannula exchange. The additional eleven days of ECMO support were uneventful. The patient was successfully bridged to long-term mechanical circulatory support. We believe that the synergistic effect of early implementation of both broad-spectrum antibiotic treatment and blood purification with the potential for rapid bacterial clearance (such as the one provided with the Seraph-100 Microbind affinity blood filter) is crucial in BSI in patients receiving advanced ECMO.

Trying to Survive A Serious Heart Condition in Time of COVID-19.

The world has suffered over the past year under COVID-19. Unfortunately, people still are getting sick from other, also severe, diseases. Although the COVID-19 infection is present, patients need treatment for other life-threatening conditions. We present the case of a 36-year-old patient with severe infective endocarditis with a large abscess of the aortic root, who also is COVID-19 positive. Definitive diagnostics and treatment were avoided due to COVID-19 infection. In the end, emergent surgery was indicated due to acute cardiac decompensation and the development of heart failure symptoms, and the patient recovered uneventfully after surgery.

Comparison between OPCABG and CABG Surgical Revascularization Using Transit Time Flow Measurement (TTFM).

OBJECTIVE: To compare the intraoperative quality of coronary anastomoses performed with or without cardiopulmonary bypass using transit time flow measurement (TTFM) parameters. METHODS: We collected data from 588 consecutive patients who underwent surgical revascularization. We retrospectively reviewed data from two groups: 411 with cardiopulmonary bypass (CABG group) and 177 off-pump (OPCABG group). Transit time flow measurement parameters: mean graft flow (MGF), pulsatile index (PI), and diastolic filing (DF) were measured for each graft and patient. RESULTS: Patients in the OPCABG group had higher EuroSCORE compared with the CABG group (3.53 ± 2.32 versus 2.84 ± 2.15, P = .002). Overall comparison of TTFM parameters showed no statistical difference between the two surgical techniques except for PI in circumflex artery territory, which was higher in the OPCABG group for all types of grafts 3.0 ± 4.9 versus 2.4 ± 2.0 in, P = .026. CONCLUSION: The comparison between OPCABG and CABG in this study showed comparable results with both surgical techniques. PI was higher in the OPCABG group in harder-to-reach vessel territories. Measurement of transit time may improve the quality, safety, and efficacy of coronary artery bypass grafting and should be considered as a routine procedure.

The epidemiological and clinical features of odontogenic infective endocarditis.

Antibiotic prophylaxis (AP) of infective endocarditis (IE) in dental practice is a controversial topic. We evaluated the characteristics of the odontogenic IE and assessed the practice and sources of information pertaining to the topic utilized by the Croatian dentists. We conducted a retrospective review of consecutive medical charts of adult patients with IE, admitted to the University Hospital for Infectious Diseases in Zagreb, Croatia, between January 2007 and December 2017. In addition, a cross-sectional, self-reporting questionnaire survey was conducted with participation of 348 Croatian dentists. Of the 811 admissions for suspected IE (40.3% of all Croatian and 92.1% of all Zagreb hospitals), 386 patients were confirmed as definite IE: 68 with odontogenic IE and 318 with IE of other origin. Their first hospital admissions were analyzed. Definite odontogenic IE was defined as a positive echocardiographic result in conjunction with two separate positive blood cultures showing exclusive oral cavity pathogen or Streptococcus viridans associated with current or recent (< 1 month) dental, periodontal, or oral cavity infection. The annual number of new odontogenic IE patients appeared constant over time. In 91.2% of the cases, odontogenic IE was not preceded by a dental procedure; poor oral health was found in 51.5% of patients, and 47.1% had no cardiac condition that increases the IE risk. In-hospital mortality was 5.1% with conservative treatment and 4.5% with cardiac surgery and was much lower for odontogenic IE than in non-odontogenic IE (14.6% and 34.4%, respectively). An increasing number of admissions for non-odontogenic IE were observed in parallel with an increasing number of staphylococcal IE. Surveyed dentists (500 invited, 69.6% responded) were aware of the AP recommendations, but were largely reluctant to treat patients at risk. In people with poor oral health, AP should be considered regardless of cardiac risk factors. Improvement of oral health should be the cornerstone of odontogenic IE prevention.

A Case of Postoperative Covid-19 Infection After Cardiac Surgery: Lessons Learned.

While the focus of the medical community is on the management of COVID-19 and its associated complex presentations, it is critical to recognize that patients will continue to present with other medical problems that require urgent therapeutic interventions. There is growing concern that such interventions might have an impact on the natural history of COVID-19. We present a case of a patient who presented with unstable angina and multivessel coronary artery disease for which coronary artery bypass surgery was indicated and performed. Unfortunately, he succumbed to respiratory complications attributed to COVID-19. Our experience suggests concern about adverse outcomes in patients undergoing cardiac surgery who might be infected with COVID-19. Clearly, additional investigations and experience are needed.

Primary Left Atrial Angiosarcoma Presenting as Acute Coronary Syndrome.

Primary cardiac neoplasms are extremely rare and often overlooked as differential diagnosis. Angiosarcomas are the most common primary malignant neoplasms of the heart often with nonspecific symptoms. We present a 43-year-old woman admitted to our hospital with chest pain and inferoposterolateral myocardial infarction. Coronary angiography indicated the distal occlusion of the left circumflex artery. Transthoracic and transoesophagic echocardiography revealed a mass in the left atrium with probable myocardial infiltration and vascularisation. The mass in the left atrium was removed by surgical resection, and histopathology confirmed angiosarcoma. We emphasize the pivotal role of transthoracic and transoesophageal echocardiography in evaluating even rare differential diagnosis of acute coronary syndrome as cardiac neoplasms.

Heart re-transplantation in Eurotransplant.

Internationally 3% of the donor hearts are distributed to re-transplant patients. In Eurotransplant, only patients with a primary graft dysfunction (PGD) within 1 week after heart transplantation (HTX) are indicated for high urgency listing. The aim of this study is to provide evidence for the discussion on whether these patients should still be allocated with priority. All consecutive HTX performed in the period 1981-2015 were included. Multivariate Cox' model was built including: donor and recipient age and gender, ischaemia time, recipient diagnose, urgency status and era. The study population included 18 490 HTX, of these 463 (2.6%) were repeat transplants. The major indications for re-HTX were cardiac allograft vasculopathy (CAV) (50%), PGD (26%) and acute rejection (21%). In a multivariate model, compared with first HTX hazards ratio and 95% confidence interval for repeat HTX were 2.27 (1.83-2.82) for PGD, 2.24 (1.76-2.85) for acute rejection and 1.22 (1.00-1.48) for CAV (P < 0.0001). Outcome after cardiac re-HTX strongly depends on the indication for re-HTX with acceptable outcomes for CAV. In contrast, just 47.5% of all hearts transplanted in patients who were re-transplanted for PGD still functioned at 1-month post-transplant. Alternative options like VA-ECMO should be first offered before opting for acute re-transplantation.

Association between Circulatory and Plaque Resistin Levels with Carotid Plaque Instability and Ischemic Stroke Events.

ses of ischemic stroke. The risk of ischemic stroke increases with the degree of carotid stenosis and plaque vulnerability. The aim of this study was to investigate the association of circulating and plaque resistin levels with plaque vulnerability and ischemic stroke events in patients with moderate- to high-grade carotid artery stenosis. METHODS: 40 patients with ischemic stroke events and 38 neurologically asymptomatic patients scheduled for carotid endarterectomy were recruited for this study. Fasting blood samples for laboratory analysis were collected preoperatively and serum resistin levels were measured by enzyme-linked immunosorbent assays. Carotid endarterectomy specimens were analyzed according to the gold-standard procedure of histological classification. Plaque resistin expression was determined by standard immunohistochemical procedure. RESULTS: Serum resistin levels and resistin plaque expression were found to be significantly higher in subjects with unstable carotid plaque (P < .001) while significantly higher serum resistin levels were also present in patients with ischemic stroke events (P < .001). In univariate stepwise logistic regression analysis, higher serum resistin levels were significantly associated with plaque instability (OR 2.223, 95% CI 1.488-3.320, P < .0001) and ischemic stroke events (OR 1.237, 95% CI 1.079-1.420, P = .002). There was also a significant association between higher serum and plaque resistin expression (OR 1.663, 95% CI1.332-2.077, P < .0001). These associations remained significant in all models of multivariate logistic regression analysis. High serum and plaque resistin levels were also significantly associated with specific histological features of plaque instability. CONCLUSION: The results suggests that serum resistin levels may be used as a potential biomarker of plaque vulnerability and ischemic stroke events in patients with moderate- to high-grade carotid artery stenosis and highlight the possible relationship that plaque resistin expression has with histological features of plaque vulnerability.

Letter from the Editor-in-Chief.

It was in the mid-nineties when a senior colleague of mine, Dr. Bojan Biocina, introduced me to something called "OpenHeart-L" on The Heart Surgery Forum website. Suddenly, a whole new world appeared in front of me! The possibility to communicate with colleagues from all around the globe was amazing. And not only that-one could ask anything, and there was always someone who had an answer, gave a piece of advice…what to do, what to avoid...it was magic! The person responsible for this whole idea of sharing information and interactive communication was Mark Levinson. At that time I was more a lurker than a poster, eagerly waiting for discussions to develop and learning from other people's posts.

HSF Meeting #3 Agenda and Abstracts

OPENING CEREMONY: I.R. Rudez and M.L. LevinsonM. Ehrlich: CELEBRATING 100 YEARS OF MEDICAL SCHOOL, UNIVERSITY OF ZAGREB.

LETTER TO THE EDITOR.

We read with great interest the report by Dr. Colak and coworkers about utilization of omentoplasty in poststernotomy mediastinitis treatment [Colak 2016]. In our opinion, several points need to be addressed.

Outcomes of Patients with Normal LDL-Cholesterol at Admission for Acute Coronary Syndromes: Lower Is Not Always Better.

BACKGROUND AND AIM: There are few prospective data on the prognostic value of normal admission low-density lipoprotein cholesterol (LDL-C) in statin-naïve patients with acute coronary syndromes (ACS) who are treated with a preemptive invasive strategy. We aimed to analyze the proportion of patients with normal LDL-C at admission for ACS in our practice, and their characteristics and clinical outcomes in comparison to patients with high admission LDL-C. PATIENTS AND METHODS: Two institutions' prospective registries of patients with confirmed ACS from Jan 2017 to Jan 2023 were used to identify 1579 statin-naïve patients with no history of prior coronary artery disease (CAD), and with available LDL-C admission results, relevant clinical and procedural data, and short- and long-term follow-up data. Normal LDL-C at admission was defined as lower than 2.6 mmol/L. All demographic, clinical, procedural, and follow-up data were compared between patients with normal LDL-C and patients with a high LDL-C level (≥2.6 mmol/L) at admission. RESULTS: There were 242 (15%) patients with normal LDL-C at admission. In comparison to patients with high LDL-cholesterol at admission, they were significantly older (median 67 vs. 62 years) with worse renal function, had significantly more cases of diabetes mellitus (DM) (26% vs. 17%), peripheral artery disease (PAD) (14% vs. 9%), chronic obstructive pulmonary disease (COPD) (8% vs. 2%), and psychological disorders requiring medical attention (19% vs. 10%). There were no significant differences in clinical type of ACS. Complexity of CAD estimated by coronary angiography was similar between the two groups (median Syntax score 12 for both groups). There were no significant differences in rates of complete revascularization (67% vs. 72%). Patients with normal LDL-C had significantly lower left ventricular ejection fraction (LVEF) at discharge (median LVEF 52% vs. 55%). Patients with normal LDL-C at admission had both significantly higher in-hospital mortality (5% vs. 2%, RR 2.07, 95% CI 1.08-3.96) and overall mortality during a median follow-up of 43 months (27% vs. 14%, RR 1.86, 95% CI 1.45-2.37). After adjusting for age, renal function, presence of diabetes mellitus, PAD, COPD, psychological disorders, BMI, and LVEF at discharge in a multivariate Cox regression analysis, normal LDL-C at admission remained significantly and independently associated with higher long-term mortality during follow-up (RR 1.48, 95% CI 1.05-2.09). CONCLUSIONS: A spontaneously normal LDL-C level at admission for ACS in statin-naïve patients was not rare and it was an independent risk factor for both substantially higher in-hospital mortality and mortality during long-term follow-up. Patients with normal LDL-C and otherwise high total cardiovascular risk scores should be detected early and treated with optimal medical therapy. However, additional research is needed to reveal all the missing pieces in their survival puzzle after ACS-beyond coronary anatomy, PCI optimization, numerical LDL-C levels, and statin therapy.

Low Level of First Morning Urine Cardiac Troponin I: A Specific Hallmark of Aortic Stenosis Severity.

Background: It has recently been shown that cardiac-specific troponin I concentrations in first morning urine samples can be measured with commercially available tests. Due to their accumulation in the first morning urine, scientific papers indicate a potential predictive value for cardiovascular diseases. Therefore, the aim of this study was to compare the concentration of cardiac troponin I in the first morning urine in patients with severe aortic stenosis and the healthy population. Patients and Methods: Blood and first morning urine samples were collected from 34 healthy individuals (17 female) at University Hospital Merkur and 25 patients with severe aortic stenosis (14 female) before surgical treatment at University Hospital Dubrava. Cardiac troponin I and T values were determined using high-sensitivity assays using commercially available Abbott and Roche tests. Results: Patients with severe aortic stenosis had significantly lower troponin I concentrations in the first morning urine samples (0.3 ng/L (0.1-0.6)) as compared to the healthy population (15.2 ng/L (8.4-19.9)) (p < 0.001). There was no statistically significant difference in troponin T concentrations between healthy individuals and patients with severe aortic stenosis. In parallel, both I and T plasma troponin concentrations were significantly higher in patients with severe aortic stenosis. Conclusions: In patients with severe aortic stenosis, cardiac troponin I values in the first morning urine are significantly lower than in healthy subjects.

Aortic Valve Repair with External Annuloplasty in Bicuspid versus Tricuspid Aortic Valve Patients.

Surgical repair for regurgitant bicuspid aortic valve (BAV) is promising but underutilized due to perceived complexities and lack of long-term data. This study evaluated the efficacy of valve-sparing root remodeling (VSRR) or isolated valve repair combined with calibrated external ring annuloplasty in BAV versus tricuspid aortic valve (TAV) patients. All patients operated on for aortic regurgitation and/or aneurysm at our institution between 2014 and 2022 were included and entered into the Aortic Valve Insufficiency and ascending aorta Aneurysm InternATiOnal Registry (AVIATOR). Patients with successful repair at index surgery (100% in the BAV group, 93% in the TAV group, p = 0.044) were included in a systemic follow-up with echocardiography at regular intervals. Among 132 patients, 58 were in the BAV (44%) and 74 in the TAV group (56%). There were no inter-group differences in preoperative patient characteristics, except BAV patients being significantly younger (47 ± 18 y vs. 60 ± 14 y, p < 0.001) and having narrower aortic roots at the level of sinuses (41 ± 6 mm vs. 46 ± 13 mm, p < 0.001) and sinotubular junctions (39 ± 10 mm vs. 42 ± 11, p = 0.032). No perioperative deaths were recorded. At four years, there was no significant difference in terms of overall survival (96.3% BAV vs. 97.2% TAV, p = 0.373), freedom from valve reintervention (85.2% BAV vs. 93.4% TAV, p = 0.905), and freedom from severe aortic regurgitation (94.1% BAV vs. 82.9% TAV, p = 0.222). Surgical repair of BAV combined with extra-aortic annuloplasty can be performed with low perioperative morbidity and mortality and excellent mid-term results which are comparable to TAV repair.

Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.

Aortic Valve Repair and Early-Career Surgeons-Nothing Is Impossible.

Aortic valve repair with either the reimplantation of the aortic valve or aortic root remodelling with the external annuloplasty procedure is the most effective means of treating aortic regurgitation and/or aortic root aneurysms [...].

A multicentre, propensity score matched analysis comparing a valve-sparing approach to valve replacement in aortic root aneurysm: Insight from the AVIATOR database.

OBJECTIVES: Our goal was to evaluate the outcome of valve-sparing root replacement (VSRR) and to compare the outcomes to those of patients having composite valve-graft conduit aortic root replacement (CVG-ARR) in a cohort of patients with aortic root aneurysm ± valve insufficiency, without valvular stenosis. Although valve-sparing procedures are preferable in young patients, there is a lack of comparative data in comparable patients. METHODS: The VSRR procedures were performed in 2005 patients, and 218 patients underwent a CVG-ARR procedure. Exclusion criteria included aortic dissection, endocarditis and valvular stenosis. Propensity score matching (3:1 ratio) was applied to compare VSRR (reimplantation 33% and remodelling 67%) and CVG-ARR. RESULTS: We matched 218 patients with CVG-ARR to 654 patients with VSRR (median age, 56.0; median follow-up was 4 years in both groups; interquartile range 1-5 years). Early mortality was 1.1% of those who had VSRR versus 2.3% in those who had CVG-ARR. Survival was 95.4% [95% confidence interval (CI) 94-97%] at 5 years in patients who had VSRR versus 85.4% (95% CI 82-92%) in those who had CVG-ARR; P = 0.002. Freedom from reintervention at 5 years was 96.8% (95% CI 95-98%) with VSRR and 95.4% (95% CI 91-99%) with CVG-ARR (P = 0.98). Additionally, there were more thromboembolic, endocarditis and bleeding events in the patients who had CVG-ARR (P = 0.02). CONCLUSIONS: This multicentre study shows excellent results after valve-sparing root replacement in patients with an ascending aortic aneurysm with or without valve insufficiency. Compared to composite valve-graft aortic root replacement, survival is better and valve-related events are fewer. Consequently, valve-sparing procedures should be considered whenever a durable repair is feasible. We advocate a valve-sparing strategy even in more complex cases when performed in experienced centres.

[Recovery after long-term pulsatile mechanical circulatory support in patient with chronic heart failure: a case report]. / Oporavak nakon dugotrajne mehanicke cirkulatorne potpore u bolesnika s kronicnim zatajivanjem srca: prikaz bolesnika.

Use of mechanical circulatory support (MCS) is a part of today's standard therapy in the treatment of end-stage heart failure. In this paper we describe characteristics of Thoratec pVAD device for MCS, implantation techniques, as well as the most important advantages and complications of application of the device. We present a 41-year-old patient with dilatated cardiomyopathy, who was the first recipient ofparacorporeal left ventricular assist device (LVAD) in the Republic of Croatia due to end-stage heart failure. After heart function recovery the patient was successfully weaned from MCS after 130 days of support.

Indications, Complications, and Outcomes of Cardiac Surgery After Heart Transplantation: Results From the Cash Study.

Background: Allograft pathologies, such as valvular, coronary artery, or aortic disease, may occur early and late after cardiac transplantation. Cardiac surgery after heart transplantation (CASH) may be an option to improve quality of life and allograft function and prolong survival. Experience with CASH, however, has been limited to single-center reports. Methods: We performed a retrospective, multicenter study of heart transplant recipients with CASH between January 1984 and December 2020. In this study, 60 high-volume cardiac transplant centers were invited to participate. Results: Data were available from 19 centers in North America (n = 7), South America (n = 1), and Europe (n = 11), with a total of 110 patients. A median of 3 (IQR 2-8.5) operations was reported by each center; five centers included ≥ 10 patients. Indications for CASH were valvular disease (n = 62), coronary artery disease (CAD) (n = 16), constrictive pericarditis (n = 17), aortic pathology (n = 13), and myxoma (n = 2). The median age at CASH was 57.7 (47.8-63.1) years, with a median time from transplant to CASH of 4.4 (1-9.6) years. Reoperation within the first year after transplantation was performed in 24.5%. In-hospital mortality was 9.1% (n = 10). 1-year survival was 86.2% and median follow-up was 8.2 (3.8-14.6) years. The most frequent perioperative complications were acute kidney injury and bleeding revision in 18 and 9.1%, respectively. Conclusion: Cardiac surgery after heart transplantation has low in-hospital mortality and postoperative complications in carefully selected patients. The incidence and type of CASH vary between international centers. Risk factors for the worse outcome are higher European System for Cardiac Operative Risk Evaluation (EuroSCORE II) and postoperative renal failure.