Objective: Patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) have a significantly increased risk to develop thoracic aortopathy. Both conditions share many... Show moreObjective: Patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) have a significantly increased risk to develop thoracic aortopathy. Both conditions share many pathophysiological mechanisms leading to aortic complications. Bicuspidy is known to have a low risk for acquired coronary artery sclerosis. The aim of this study is to determine the risk of coronary sclerosis in MFS patients. Methods: Marfan syndrome patients with an aortic root dilatation, which were surgically treated between 1999 and 2017, were included and matched with BAV and tricuspid aortic valves (TAV) patients based on sex and age. Cardiovascular risk profiles were determined in all three groups. Coronary sclerosis was graded in all patients on coronary imaging (coronary angiography or computed tomography) using a coronary artery scoring method, which divides the coronaries in 28 segments and scores non-obstructive (20-49% sclerosis) and obstructive coronary sclerosis (>49% sclerosis) in each segment. Results: A total of 90 matched patients (30 within each group) were included. MFS patients showed less cardiovascular risk factors compared to BAV and TAV patients. TAV patients had higher amounts of obstructive coronary sclerosis as compared to BAV patients (p = 0.039) and MFS patients (p = 0.032). No difference in non- and obstructive coronary artery disease (CAD) was found between the MFS and BAV population. Conclusion: Marfan syndrome and bicuspid aortic valve patients have a significantly lower risk for, and prevalence of CAD as compared to TAV individuals. Show less
Dolmaci, O.B.; Mathari, S. el; Driessen, A.H.G.; Klautz, R.J.M.; Poelmann, R.E.; Lindeman, J.H.N.; Grewal, N. 2023
Objectives: Abdominal aortic aneurysms are associated with a sharply increased cardiovascular risk. Cardiovascular risk management is therefore recommended in prevailing guidelines for abdominal... Show moreObjectives: Abdominal aortic aneurysms are associated with a sharply increased cardiovascular risk. Cardiovascular risk management is therefore recommended in prevailing guidelines for abdominal aneurysm patients. It has been hypothesized that associated risk relates to loss of aortic compliance. If this hypothesis is correct, observations for abdominal aneurysms would also apply to thoracic aortic aneurysms. The objective of this study is to test whether thoracic aneurysms are also associated with an increased cardiovascular risk burden. Methods: Patients who underwent aortic valve or root surgery were included in the study (n = 239). Cardiovascular risk factors were studied and atherosclerosis was scored based on the preoperative coronary angiographies. Multivariate analyses were performed, controlling for cardiovascular risk factors and aortic valve morphology. Comparisons were made with the age- and gender-matched general population and non-aneurysm patients as control groups. A thoracic aortic aneurysm was defined as an aortic aneurysm of >= 45 mm. Results: Thoracic aortic aneurysm was not associated with an increased coronary atherosclerotic burden (p = 0.548). Comparison with the general population revealed a significantly higher prevalence of hypertension (61.4% vs. 32.2%, p < 0.001) and a lower prevalence of diabetes (1.4% vs. 13.1%, p = 0.001) in the thoracic aneurysm group. Conclusions: The extreme cardiovascular risk associated with abdominal aortic aneurysms is location-specific and not explained by loss of aortic compliance. Thoracic aortic aneurysm, in contrast to abdominal, is not part of the atherosclerotic disease spectrum and, therefore, cardiovascular risk management does not need to be implemented in treatment guidelines of isolated thoracic aneurysms. Hypertension should be treated. Show less
Growing interest in minimalizing surgical trauma during heart procedures stimulated the development of robotic mitral valve surgery in the late 1990s. Initially, the new technology was slowly... Show moreGrowing interest in minimalizing surgical trauma during heart procedures stimulated the development of robotic mitral valve surgery in the late 1990s. Initially, the new technology was slowly adopted in clinical practice. However, following encouraging results by teams that adopted robotic heart surgery early on, a growing interest in implementation of robotic mitral valve surgery has emerged. Of importance are the technical developments and possibilities that accompany robotic surgery.Robotic arms feature unique characteristics, allowing unparalleled range of motion and allowing complex mitral valve repair techniques to be performed without limitations related to limited surgical incisions. High-quality three-dimensional vision effectively compensates for the lack of tactile feedback.Several technical solutions have been developed to facilitate mitral valve repair in minimal invasive setting, including chordal guiding systems, now available with various annuloplasty rings. On the other hand, precise vision and movements allows accurate determination of the length of implanted neochordae, facilitating precise determination of the length of implanted neochords even without the use of chordal-guiding systems. With robotic mitral valve surgery, leaflet resection techniques can be performed without limitations, ensuring that no compromises of the surgical strategy are made. Nevertheless, careful preoperative planning with appropriate work-up and imaging is of utmost importance to prevent complications. Moreover, the drawbacks of the initial learning curve and higher procedural costs are counterbalanced by less surgical trauma, lower utilization of blood products, and faster patient recovery. Robotic mitral valve surgery is still a young field and evolving technology that is bound to become an important tool in the toolbox of surgical mitral valve approaches. Show less
Objective: Posterior mitral valve leaflet prolapse repair can be performed by leaflet resection or chordal replacement techniques. The impact of these techniques on left ventricular function... Show moreObjective: Posterior mitral valve leaflet prolapse repair can be performed by leaflet resection or chordal replacement techniques. The impact of these techniques on left ventricular function remains a topic of debate, considering the presumed better preservation of mitral-ventricular continuity when leaflet resection is avoided. We explored the effect of different posterior mitral valve leaflet repair techniques on postoperative left ventricular function. Methods: In total, 125 patients were included and divided into 2 groups: leaflet resection (n=82) and isolated chordal replacement (n=43). Standard and advanced echocardiographic assessments were performed preoperatively, directly postoperatively, and at late follow-up. In addition, left ventricular global longitudinal strain was measured and corrected for left ventricular end-diastolic volume to adjust for the significant changes in left ventricular volumes. Results: At baseline, no significant intergroup difference in left ventricular function was observed measured with the corrected left ventricular global longitudinal strain (resect: 1.76% +/- 0.58%/10 mL vs respect: 1.70% +/- 0.57%/10 mL, P=.560). Postoperatively, corrected left ventricular global longitudinal strain worsened in both groups but improved significantly during late follow-up, returning to preoperative values (resect: 1.39% +/- 0.49% to 1.71% +/- 0.56%/10 mL, P<.001 and respect: 1.30% +/- 0.45% to 1.70% +/- 0.54%/10 mL, P<.001). Mixed model analysis showed no significant effect on the corrected left ventricular global longitudinal strain when comparing the 2 different surgical repair techniques over time (P=.943). Conclusions: Our study showed that both leaflet resection and chordal replacement repair techniques are effective at preserving postoperative left ventricular function in patients with posterior mitral valve leaflet prolapse and significant regurgitation. Show less
ObjectivePosterior mitral valve leaflet prolapse repair can be performed by leaflet resection or chordal replacement techniques. The impact of these techniques on left ventricular function remains... Show moreObjectivePosterior mitral valve leaflet prolapse repair can be performed by leaflet resection or chordal replacement techniques. The impact of these techniques on left ventricular function remains a topic of debate, considering the presumed better preservation of mitral-ventricular continuity when leaflet resection is avoided. We explored the effect of different posterior mitral valve leaflet repair techniques on postoperative left ventricular function.MethodsIn total, 125 patients were included and divided into 2 groups: leaflet resection (n = 82) and isolated chordal replacement (n = 43). Standard and advanced echocardiographic assessments were performed preoperatively, directly postoperatively, and at late follow-up. In addition, left ventricular global longitudinal strain was measured and corrected for left ventricular end-diastolic volume to adjust for the significant changes in left ventricular volumes.ResultsAt baseline, no significant intergroup difference in left ventricular function was observed measured with the corrected left ventricular global longitudinal strain (resect: 1.76% ± 0.58%/10 mL vs respect: 1.70% ± 0.57%/10 mL, P = .560). Postoperatively, corrected left ventricular global longitudinal strain worsened in both groups but improved significantly during late follow-up, returning to preoperative values (resect: 1.39% ± 0.49% to 1.71% ± 0.56%/10 mL, P < .001 and respect: 1.30% ± 0.45% to 1.70% ± 0.54%/10 mL, P < .001). Mixed model analysis showed no significant effect on the corrected left ventricular global longitudinal strain when comparing the 2 different surgical repair techniques over time (P = .943).ConclusionsOur study showed that both leaflet resection and chordal replacement repair techniques are effective at preserving postoperative left ventricular function in patients with posterior mitral valve leaflet prolapse and significant regurgitation. Show less
Introduction Vasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac... Show moreIntroduction Vasoplegia is a common complication after cardiac surgery and is associated with poor prognosis. It is characterised by refractory hypotension despite normal or even increased cardiac output. The pathophysiology is complex and includes the systemic inflammatory response caused by cardiopulmonary bypass (CPB) and surgical trauma. Patients with end-stage heart failure (HF) are at increased risk for developing vasoplegia. The CytoSorb adsorber is a relatively new haemoadsorption device which can remove circulating inflammatory mediators in a concentration based manner. The CytoSorb-HF trial aims to evaluate the efficacy of CytoSorb haemoadsorption in limiting the systemic inflammatory response and preventing postoperative vasoplegia in HF patients undergoing cardiac surgery with CPB. Methods and analysis This is an investigator-initiated, single-centre, randomised, controlled clinical trial. In total 36 HF patients undergoing elective cardiac surgery with an expected CPB duration of more than 120 min will be randomised to receive CytoSorb haemoadsorption along with standard surgical treatment or standard surgical treatment alone. The primary endpoint is the change in systemic vascular resistance index with phenylephrine challenge after CPB. Secondary endpoints include inflammatory markers, sublingual microcirculation parameters and 30-day clinical indices. In addition, we will assess the cost-effectiveness of using the CytoSorb adsorber. Vascular reactivity in response to phenylephrine challenge will be assessed after induction, after CPB and on postoperative day 1. At the same time points, and before induction and on postoperative day 4 (5 time points in total), blood samples will be collected and the sublingual microcirculation will be recorded. Study participants will be followed up until day 30.Ethics and dissemination The trial protocol was approved by the Medical Ethical Committee of Leiden The Hague Delft (METC LDD, registration number P20.039). The results of the trial will be published in peer-reviewed medical journals and through scientific conferences. Show less
Objectives: Although the impact of prosthesis-patient mismatch (PPM) on survival has been widely studied, there has been little debate about whether the current definition of PPM truly reflects... Show moreObjectives: Although the impact of prosthesis-patient mismatch (PPM) on survival has been widely studied, there has been little debate about whether the current definition of PPM truly reflects hemodynamic obstruction. This study aimed to validate the categorization of indexed effective orifice area (EOAi) for the classification of PPM.Methods: In total, 2171 patients who underwent aortic valve replacement with a surgical stented bioprosthesis in 5 trials (CoreValve US High-Risk, SURTAVI [Surgical Replacement and Transcatheter Aortic Valve Implantation Trial], Evolut Low Risk, PERIGON [PERIcardial SurGical AOrtic Valve ReplacemeNt] Pivotal Trial for the Avalus valve, and PERIGON Japan) were used for this analysis. The echocardiographic images at the 1-year follow-up visit were evaluated to explore the association between EOAi and mean aortic gradient and its interaction with other patient characteristics, including obesity. In addition, different criteria of PPM were compared with reflect elevated mean aortic gradients (>= 20 mm Hg).Results: A relatively smaller exponential decay in mean aortic gradient was found for increasing EOAi, as the slope on the log scale was -0.83 versus -2.5 in the publication from which the current cut-offs for PPM originate. The accuracy of the American Society of Echocardiography, Valve Academic Research Consortium-2, and European Association of Cardiovascular Imaging definitions of PPM to reflect elevated mean aortic gradients was 49%, 57%, and 57%, respectively. The relation between EOAi and mean aortic gradient was not significantly different between obese and non-obese patients (P = .20).Conclusions: The use of EOAi thresholds to classify patients with PPM is undermined by a less-pronounced exponential relationship between EOAi and mean aortic gradient than previously demonstrated. Moreover, recent adjustment for obesity in the definition of PPM is not supported by these data. Show less
OBJECTIVES This analysis evaluated the safety, durability and haemodynamic performance of a stented bovine pericardial valve through 5 years of follow-up in patients with an indication for surgical... Show moreOBJECTIVES This analysis evaluated the safety, durability and haemodynamic performance of a stented bovine pericardial valve through 5 years of follow-up in patients with an indication for surgical aortic valve replacement.METHODS Kaplan-Meier analysis was used to estimate the incidence of survival and valve-related thromboembolism, major paravalvular leak, endocarditis, structural valve deterioration (SVD) and reintervention. The mean aortic gradient and New York Heart Association (NYHA) functional class were also evaluated.RESULTS A total of 1118 patients have received the Avalus valve; 564 have completed the 5-year follow-up. The median follow-up was 4.85 years (4810 patient-years total follow-up). At baseline, the mean age was 70.2 +/- 9.0 years; 75.1% of patients were male. The Society of Thoracic Surgeons predicted risk of mortality was 2.0 +/- 1.4%. Most patients were in NYHA functional class II (46.8%) or III (40.3%). At the 5-year follow-up, the overall Kaplan-Meier survival rate was 88.1% (85.9-90.0%). The Kaplan-Meier event rates were 5.6% (4.3-7.2%) for thromboembolism, 4.4% (3.2-6.0%) for endocarditis, 0.2% (0.0-0.7%) for a major paravalvular leak and 3.2% (2.3-4.6%) for reintervention. There were no cases of SVD. The mean gradient decreased from 42.1 +/- 17.1 mmHg at baseline, to 13.1 +/- 4.7 mmHg at discharge and remained stable at 12.5 +/- 4.6 mmHg at 5 years. More than 95% of patients were in NYHA functional class I/II 5 years after surgery.CONCLUSIONS The findings of a high survival rate, excellent safety, no SVD and stable haemodynamic performance and functional status through 5 years of follow-up are encouraging. Additional follow-up is needed to assess the long-term durability of this contemporary surgical bioprosthesis. Show less
OBJECTIVESThis analysis evaluated the safety, durability and haemodynamic performance of a stented bovine pericardial valve through 5 years of follow-up in patients with an indication for surgical... Show moreOBJECTIVESThis analysis evaluated the safety, durability and haemodynamic performance of a stented bovine pericardial valve through 5 years of follow-up in patients with an indication for surgical aortic valve replacement.METHODSKaplan–Meier analysis was used to estimate the incidence of survival and valve-related thromboembolism, major paravalvular leak, endocarditis, structural valve deterioration (SVD) and reintervention. The mean aortic gradient and New York Heart Association (NYHA) functional class were also evaluated.RESULTSA total of 1118 patients have received the Avalus valve; 564 have completed the 5-year follow-up. The median follow-up was 4.85 years (4810 patient-years total follow-up). At baseline, the mean age was 70.2 ± 9.0 years; 75.1% of patients were male. The Society of Thoracic Surgeons predicted risk of mortality was 2.0 ± 1.4%. Most patients were in NYHA functional class II (46.8%) or III (40.3%). At the 5-year follow-up, the overall Kaplan–Meier survival rate was 88.1% (85.9–90.0%). The Kaplan–Meier event rates were 5.6% (4.3–7.2%) for thromboembolism, 4.4% (3.2–6.0%) for endocarditis, 0.2% (0.0–0.7%) for a major paravalvular leak and 3.2% (2.3–4.6%) for reintervention. There were no cases of SVD. The mean gradient decreased from 42.1 ± 17.1 mmHg at baseline, to 13.1 ± 4.7 mmHg at discharge and remained stable at 12.5 ± 4.6 mmHg at 5 years. More than 95% of patients were in NYHA functional class I/II 5 years after surgery.CONCLUSIONSThe findings of a high survival rate, excellent safety, no SVD and stable haemodynamic performance and functional status through 5 years of follow-up are encouraging. Additional follow-up is needed to assess the long-term durability of this contemporary surgical bioprosthesis. Show less
Study objective: The added value of computed tomography (CT) follow-up after elective proximal aortic surgery is unclear. We evaluated the benefit of CT follow-up by assessing the incidence of... Show moreStudy objective: The added value of computed tomography (CT) follow-up after elective proximal aortic surgery is unclear. We evaluated the benefit of CT follow-up by assessing the incidence of aorta-related complications and reinterventions detected during routine CT follow-up. Methods: Data on 314 patients undergoing first time elective proximal aortic surgery between 2000 and 2015 were collected. The primary study end points were aorta-related complications and reinterventions, detected during routine CT follow-up. Secondary study endpoints included all aorta-related complications and reinterventions, irrespective of the mode of detection and survival. Results: Median CT follow-up time was 6.8 (IQR 4.1-9.8) years, during which a total of 1303 routine follow-up CT-scans (median 4, IQR 3-5) were performed. During CT follow-up, aorta-related complications were detected in 18 (5.7%) patients, of which 6 (1.6%) underwent reintervention. In total, 28 aorta-related complications were observed in 23 (7.3%) patients, of which 9 led to reintervention. In order to detect 1 aorta-related complication leading to reintervention, 218 routine followup CT-scans were required. The unadjusted and EuroSCORE II adjusted hazard ratios of not undergoing CT follow-up on mortality were 1.260 (95% CI 0.705-2.251) and 0.830 (95% CI 0.430-1.605), respectively. Conclusions: Following first time elective proximal aor tic surgery, aor ta-related complications are uncommon, are not always detected during CT follow-up and, if detected, often do not result in reintervention. Therefore, a more conservative CT follow-up protocol could be considered in selected patients to reduce lifetime radiation burden and health care costs. Show less
The optimal choice of graft material in patients >= 70 years of age undergoing coronary artery bypass grafting remains unknown. A systematic review of literature was conducted by searching... Show moreThe optimal choice of graft material in patients >= 70 years of age undergoing coronary artery bypass grafting remains unknown. A systematic review of literature was conducted by searching PubMed, Embase, Web of Science, and Cochrane Library databases for original publications that compared bilateral internal thoracic artery (BITA) grafting with single internal thoracic artery grafting in patients >= 70 years of age. Data were extracted by 2 independent investigators and meta-analyzed with the use of random effects. A total of 10 studies, including 11,185 patients, met the inclusion criteria. No differences in early mortality and morbidity, with the exemption of sternal wound complications which were more frequently observed in the BITA group (odds ratio 1.72, 95% 1.00 to 2.96 confidence interval [CI], p = 0.05; propensity score-matched population odds ratio 1.58, 95% CI 1.09 to 2.29, p = 0.02), were observed. Overall survival was superior in the overall patient popu-lation (hazard ratio [HR] 0.76, 95% CI 0.66 to 0.86, p < 0.001), after applying a blanking period of 3 months to the overall patient population (HR 0.77, 95% CI 0.64 to 0.92, p = 0.005) as well as in the matched population (HR 0.72, 95% CI 0.58 to 0.89, p = 0.002); in all cases, a benefit was readily seen within a few years after surgery. The difference in freedom from major adverse cardiac and cerebrovascular events failed to reach statistical significance (overall patient population HR 0.55, 95% CI 0.27 to 1.13, p = 0.10; matched population HR 0.52, 95% CI 0.23 to 1.16, p = 0.11). In conclusion, BITA grafting can be safely performed in patients >= 70 years of age as late clinical benefits are expected to mani-fest themselves readily within a few years after surgery. (C) 2022 The Author(s). Published by Elsevier Inc. Show less
Background: The advent of transcatheter aortic valve replacement (AVR) has led to an increased emphasis on reducing the invasiveness of surgical procedures. The aim of this study was to evaluate... Show moreBackground: The advent of transcatheter aortic valve replacement (AVR) has led to an increased emphasis on reducing the invasiveness of surgical procedures. The aim of this study was to evaluate clinical outcomes and hemodynamic performance achieved with minimally invasive aortic valve replacement (MI-AVR) as compared with conventional AVR. Methods: Patients who underwent surgical AVR with the Avalus bioprosthesis, as part of a prospective multicenter non-randomized trial, were included in this analysis. Surgical approach was left to the discretion of the surgeons. Patient characteristics and clinical outcomes were compared between MI-AVR and conventional AVR groups in the entire cohort ( n = 1077) and in an isolated AVR subcohort ( n = 528). Propensity score adjustment was performed to estimate the effect of MI-AVR on adverse events. Results: Patients treated with MI-AVR were younger, had lower STS scores, and underwent concomitant procedures less often. Valve size implanted was comparable between the groups. MI-AVR was associated with longer procedural times in the isolated AVR subcohort. Postprocedural hemodynamic performance was comparable. There were no significant differences between MI-AVR and conventional AVR in early and 3-year all-cause mortality, thromboembolism, reintervention, or a composite of those endpoints within either the entire cohort or the isolated AVR subcohort. After propensity score adjustment, there remained no association between MI-AVR and the composite endpoint (hazard ratio: 0.86, 95% confidence interval: 0.47-1.55, p = 0.61). Conclusion: Three-year outcomes after MI-AVR with the Avalus bioprosthetic valve were comparable to conventional AVR. These results provide important insights into the overall ability to reduce the invasiveness of AVR without compromising outcomes. Show less
Background The advent of transcatheter aortic valve replacement (AVR) has led to an increased emphasis on reducing the invasiveness of surgical procedures. The aim of this study was to evaluate... Show moreBackground The advent of transcatheter aortic valve replacement (AVR) has led to an increased emphasis on reducing the invasiveness of surgical procedures. The aim of this study was to evaluate clinical outcomes and hemodynamic performance achieved with minimally invasive aortic valve replacement (MI-AVR) as compared with conventional AVR.Methods Patients who underwent surgical AVR with the Avalus bioprosthesis, as part of a prospective multicenter non-randomized trial, were included in this analysis. Surgical approach was left to the discretion of the surgeons. Patient characteristics and clinical outcomes were compared between MI-AVR and conventional AVR groups in the entire cohort (n = 1077) and in an isolated AVR subcohort (n = 528). Propensity score adjustment was performed to estimate the effect of MI-AVR on adverse events.Results Patients treated with MI-AVR were younger, had lower STS scores, and underwent concomitant procedures less often. Valve size implanted was comparable between the groups. MI-AVR was associated with longer procedural times in the isolated AVR subcohort. Postprocedural hemodynamic performance was comparable. There were no significant differences between MI-AVR and conventional AVR in early and 3-year all-cause mortality, thromboembolism, reintervention, or a composite of those endpoints within either the entire cohort or the isolated AVR subcohort. After propensity score adjustment, there remained no association between MI-AVR and the composite endpoint (hazard ratio: 0.86, 95% confidence interval: 0.47–1.55, p = 0.61).Conclusion Three-year outcomes after MI-AVR with the Avalus bioprosthetic valve were comparable to conventional AVR. These results provide important insights into the overall ability to reduce the invasiveness of AVR without compromising outcomes. Show less
A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac anomaly, in which the valve has only two leaflets, instead of the normal three. Patients with a BAV have an increased risk of... Show moreA bicuspid aortic valve (BAV) is the most prevalent congenital cardiac anomaly, in which the valve has only two leaflets, instead of the normal three. Patients with a BAV have an increased risk of aneurysm formation and the development of an aortic dissection. Vascular smooth muscle cells in both the non-and dilated aortic wall are characterized by a maturation defect in all BAV patients, as compared to patients with a tricuspid aortic valve, which can contribute to inherent developmental susceptibility. Besides structural abnormalities of the vascular wall, a turbulent blood flow, caused by bicuspid valve geometry, could expedite the pathological process in the aortic wall, leading to aortopathy. Although the risk for aortopathy is significant, not all BAV patients experience (acute) aortic complications in their lifespan, highlighting the complexity of the pathogenetic process. Recent studies have focused on the embryonic development of semilunar valves and the ascending aortic wall. Their findings highlight that a defect in the embryogenesis could not only explain the development of a malformed aortic valve but also the increased risk for ascending aorta and arch pathology. This review presents an overview of the normal and abnormal development of the aortic valve and the aortic wall: a common defect in early embryogenesis causes the development of a BAV and associated aortopathy. Show less
Functional human atrial myocytes derived from foetal atrial tissue can be massively expanded via a conditional cell-immortalization method, and used in in vitro models of atrial fibrillation.The... Show moreFunctional human atrial myocytes derived from foetal atrial tissue can be massively expanded via a conditional cell-immortalization method, and used in in vitro models of atrial fibrillation.The lack of a scalable and robust source of well-differentiated human atrial myocytes constrains the development of in vitro models of atrial fibrillation (AF). Here we show that fully functional atrial myocytes can be generated and expanded one-quadrillion-fold via a conditional cell-immortalization method relying on lentiviral vectors and the doxycycline-controlled expression of a recombinant viral oncogene in human foetal atrial myocytes, and that the immortalized cells can be used to generate in vitro models of AF. The method generated 15 monoclonal cell lines with molecular, cellular and electrophysiological properties resembling those of primary atrial myocytes. Multicellular in vitro models of AF generated using the immortalized atrial myocytes displayed fibrillatory activity (with activation frequencies of 6-8 Hz, consistent with the clinical manifestation of AF), which could be terminated by the administration of clinically approved antiarrhythmic drugs. The conditional cell-immortalization method could be used to generate functional cell lines from other human parenchymal cells, for the development of in vitro models of human disease. Show less
BackgroundDestination left ventricular assist device placement is increasing as a result of donor shortages and changing patient attitudes. As organ shortages become critical, LVAD programs become... Show moreBackgroundDestination left ventricular assist device placement is increasing as a result of donor shortages and changing patient attitudes. As organ shortages become critical, LVAD programs become fundamental even in more remote regions of the world including island states. Here, we provide a look into the current state and availability of LVAD programs in island states.Main bodyA narrative review was performed using the World Health Organization Global Index Medicus and PubMed/MEDLINE databases to identify articles describing the island states having reported LVAD placements and programs. Additionally, INTERMACS reports were used. Data were retrieved and a review is presented describing the current state of LVADs in island states. The Caribbean region as a whole has a heart failure (HF) prevalence of 814 per 100,000 and Oceania 667 per 100,000 people. We estimate that over 3000 people in these islands need either a heart transplant or an LVAD.Short conclusionFor HF patients living in island regions, special attention should be paid to the inability of having access to specialized mainland medical care. The continuous quest for a solution to HF in island regions should include the establishing of high-quality LVAD programs in a transfer-network centralized/regionalized system to care for those patients not candidates for long-distance air-bridging. Show less