Massive Parallel DNA Sequencing of Patients with Inherited Cardiomyopathies in Cyprus and Suggestion of Digenic or Oligogenic Inheritance.

Inherited cardiomyopathies represent a highly heterogeneous group of cardiac diseases. DNA variants in genes expressed in cardiomyocytes cause a diverse spectrum of cardiomyopathies, ultimately leading to heart failure, arrythmias, and sudden cardiac death. We applied massive parallel DNA sequencing using a 72-gene panel for studying inherited cardiomyopathies. We report on variants in 25 families, where pathogenicity was predicted by different computational approaches, databases, and an in-house filtering analysis. All variants were validated using Sanger sequencing. Familial segregation was tested when possible. We identified 41 different variants in 26 genes. Analytically, we identified fifteen variants previously reported in the Human Gene Mutation Database: twelve mentioned as disease-causing mutations (DM) and three as probable disease-causing mutations (DM?). Additionally, we identified 26 novel variants. We classified the forty-one variants as follows: twenty-eight (68.3%) as variants of uncertain significance, eight (19.5%) as likely pathogenic, and five (12.2%) as pathogenic. We genetically characterized families with a cardiac phenotype. The genetic heterogeneity and the multiplicity of candidate variants are making a definite molecular diagnosis challenging, especially when there is a suspicion of incomplete penetrance or digenic-oligogenic inheritance. This is the first systematic study of inherited cardiac conditions in Cyprus, enabling us to develop a genetic baseline and precision cardiology.

Synchronous Left Ventricular and Endocranial Mass.

Myocardial cysts represent a miscellaneous and infrequent spectrum of conditions, with each of them coming from a different etiological background. Congenital myocardial cysts, neoplasia, cysts of infectious origin (bacterial, viral, or parasitic), and cardiac pathologies that may fake cystic content are all encompassed in this group. Although most patients are asymptomatic, some may occasionally present with obstruction, valvular dysfunction, or heart failure. Even more uncommon is the coexistence of a myocardial cyst with other extracardiac locations causing extracardiac symptoms. In this direction, the coexistence of a myocardial and endocranial cyst is extremely rare and can cause symptomatology from the affected organs (e.g., seizures). Cardiac investigation in this context is mainly dependent on non-invasive diagnostic modalities, and laboratory procedures. In this case report, we present a 26-year-old Congolese male admitted with dyspnea and epileptic seizures. Echocardiography revealed left ventricular and both mitral and tricuspid valve dysfunction and the presence of two myocardial cysts, while brain computed tomography showed an additional frontal cystic lesion. A precise diagnostic workup with a combination of non-invasive imaging, laboratory results, and epidemiology data assisted the diagnosis and guided the most suitable therapeutic choice.

Myocarditis Related to the Use of Mesalazine.

Myocarditis is a rare complication of therapy with mesalazine, a drug traditionally used in the treatment of inflammatory bowel disease. We report a case of a 32-year-old man with a recent diagnosis of ulcerative colitis, who presented to our hospital with chest pain and elevated troponin, 12 days following initiation of mesalazine. Diagnosis of myocarditis was confirmed with cardiac magnetic resonance imaging (CMR), which showed subepicardial gadolinium enhancement in the basal lateral/inferolateral segment of the heart. The patient's clinical condition improved upon stopping mesalazine and the follow-up CMR demonstrated resolution of the previous findings. Mesalazine can cause myocarditis early after initiation and clinicians should be aware of this rare yet serious cardiotoxic effect, as the discontinuation of the medication is the mainstay of treatment and leads to significant recovery.

Case report: Aborted sudden cardiac death as a first presentation of severe mitral annulus disjunction-a case series and review of the literature.

Mitral annulus disjunction (MAD) is defined as a systolic displacement between the ventricular myocardium and the posterior mitral annulus supporting the posterior mitral leaflet. This structural abnormality is associated with the loss of mechanical annular function manifested as an abnormal systolic excursion of the leaflet hinge point into the left atrium but with maintained electrical function, separating the left atrium and ventricle electrophysiologically. The mitro-aortic fibrous continuity limits MAD anteriorly, between the aortic cusps and the anterior leaflet of the mitral valve. Consequently, MAD has been observed only at the insertion of the posterior leaflet. It can extend preferentially at the central posterior scallop. The first diagnostic modality aiding the diagnosis is transthoracic echocardiography (TTE), although in some cases adjunctive cardiac imaging modality might be suggested. MAD carries a strong association with malignant ventricular arrhythmogenesis and a profound predisposition for sudden cardiac death (SCD). In this context, a thorough investigation of this morphological and functional abnormality is vital in estimating the risk assessment and stratification for optimal management and elimination of the risk of the patient for SCD. Based on the current scientific data and literature, we will discuss the diagnosis, clinical implications, risk stratification, and therapeutic management of MAD.

MEDEA randomised intervention study protocol in Cyprus, Greece and Israel for mitigation of desert dust health effects in adults with atrial fibrillation.

INTRODUCTION: Mediterranean countries experience frequent desert dust storm (DDS) events originating from neighbouring Sahara and Arabian deserts, which are associated with significant increase in mortality and hospital admissions, mostly from cardiovascular and respiratory diseases. Short-term exposure to ambient air pollution is considered as a trigger for symptomatic exacerbations of pre-existing paroxysmal atrial fibrillation (AF) and other types of heart arrhythmia. The Mitigating the Health Effects of Desert Dust Storms Using Exposure-Reduction Approaches clinical randomised intervention study in adults with AF is funded by EU LIFE+programme to evaluate the efficacy of recommendations aiming to reduce exposure to desert dust and related heart arrhythmia effects. METHODS AND ANALYSIS: The study is performed in three heavily exposed to desert dust regions of the Eastern Mediterranean: Cyprus, Israel and Crete-Greece. Adults with paroxysmal AF and implanted pacemaker are recruited and randomised to three parallel groups: (a) no intervention, (b) interventions to reduce outdoor exposure to desert dust, (c) interventions to reduce both outdoor and indoor exposure to particulate matter during desert dust episodes. Eligible participants are enrolled on a web-based platform which communicates, alerts and makes exposure reduction recommendations during DDS events. Exposure changes are assessed by novel tools (smartwatches with Global Positioning System and physical activity sensors, air pollution samplers assessing air quality inside and outside participant's homes, etc). Clinical outcomes include the AF burden expressed as the percentage of time with paroxysmal AF over the total study period, the incidence of ventricular arrhythmia episodes as recorded by the participants' pacemakers or cardioverters/defibrillators and the disease-specific Atrial Fibrillation Effect on QualiTy-of-Life questionnaire. ETHICS AND DISSEMINATION: Local bioethics' authorities approved the study at all sites, according to national legislations (Cyprus: National Bioethics Committee, Data Protection Commissioner and Ministry of Health; Greece, Scientific Committee and Governing Board of the University General Hospital of Heraklion; Israel: Institutional Review Board ('Helsinki committee') of the Soroka University Medical Center). The findings will be publicised in peer-reviewed scientific journals, in international conferences and in professional websites and newsletters. A summary of the results and participants' interviews will be included in a documentary in English, Greek and Hebrew. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier; NCT03503812.

The Conjunction Conundrum in Transcatheter Aortic Valve Implantation.

A continuous discussion regarding the predictors for permanent pacemaker implantation (PPI) following transcatheter aortic valve implantation (TAVI) is ongoing, especially in the era of low and medium risk patients. The aim of this article is to review the data so far regarding the pathophysiology, risk factors, and the indications for permanent pacemaker implantation after TAVI. The factors that contribute to rhythm abnormalities post TAVI can be divided into pre-existing conduction abnormalities, patient-related anatomical factors, and peri-procedural technical factors. The latter components are potentially modifiable, and this is where attention should be directed, particularly now that in an era of TAVI expansion towards lower-risk patients.

Improved indoor air quality during desert dust storms: The impact of the MEDEA exposure-reduction strategies.

Desert dust storms (DDS) are natural events that impact not only populations close to the emission sources but also populations many kilometers away. Countries located across the main dust sources, including countries in the Eastern Mediterranean, are highly affected by DDS. In addition, climate change is expanding arid areas exacerbating DDS events. Currently, there are no intervention measures with proven, quantified exposure reduction to desert dust particles. As part of the wider "MEDEA" project, co-funded by LIFE 2016 Programme, we examined the effectiveness of an indoor exposure-reduction intervention (i.e., decrease home ventilation during DDS events and continuous use of air purifier during DDS and non-DDS days) across homes and/or classrooms of schoolchildren with asthma and adults with atrial fibrillation in Cyprus and Crete-Greece. Participants were randomized to a control or intervention groups, including an indoor intervention group with exposure reduction measures and the use of air purifiers. Particle sampling, PM10 and PM2.5, was conducted in participants' homes and/or classrooms, between 2019 and 2022, during DDS-free weeks and during DDS days for as long as the event lasted. In indoor and outdoor PM10 and PM2.5 samples, mass and content in main and trace elements was determined. Indoor PM2.5 and PM10 mass concentrations, adjusting for premise type and dust conditions, were significantly lower in the indoor intervention group compared to the control group (PM2.5-intervention/PM2.5-control = 0.57, 95% CI: 0.47, 0.70; PM10-intervention/PM10-control = 0.59, 95% CI: 0.49, 0.71). In addition, the PM2.5 and PM10 particles of outdoor origin were significantly lower in the intervention vs. the control group (PM2.5 infiltration intervention-to-control ratio: 0.49, 95% CI: 0.42, 0.58; PM10 infiltration intervention-to-control ratio: 0.68, 95% CI: 0.52, 0.89). Our findings suggest that the use of air purifiers alongside decreased ventilation measures is an effective protective measure that reduces significantly indoor exposure to particles during DDS and non-DDS in high-risk population groups.

Role of inflammation following an acute myocardial infarction: design of INFINITY.

After a myocardial infarction, the inflammatory response is connected to major adverse outcomes such as ischemia-reperfusion injury, adverse cardiac remodeling, infarct size and poor prognosis. INFlammatIoN amI sTudY (INFINITY) is a multicenter, prospective, observational, cohort study designed to investigate the prognostic role of the cytokines IL-6, IL-10, IL-18 and IL-17 and the adipokines leptin, apelin and chemerin in patients with acute coronary syndrome. The study will test if these inflammatory biomarkers reflect different clinical manifestations of coronary artery disease and have a prognostic role in a 6-month follow-up period. This study represents an opportunity to investigate further the prognostic role of a selected combination of proinflammatory and anti-inflammatory biomarkers in the prognosis and risk stratification of acute coronary syndrome patients.

Personalised Treatment in Aortic Stenosis: A Patient-Tailored Transcatheter Aortic Valve Implantation Approach.

Transcatheter aortic valve replacement (TAVI) has become a game changer in the management of severe aortic stenosis shifting the concept from inoperable or high-risk patients to intermediate or low surgical-risk individuals. Among devices available nowadays, there is no clear evidence that one device is better than the other or that one device is suitable for all patients. The selection of the optimal TAVI valve for every patient represents a challenging process for clinicians, given a large number of currently available devices. Consequently, understanding the advantages and disadvantages of each valve and personalising the valve selection based on patient-specific clinical and anatomical characteristics is paramount. This review article aims to both analyse the available devices in the presence of specific clinical and anatomic features and offer guidance to select the most suitable valve for a given patient.

Influence of the Second Wave of the COVID-19 Pandemic on the Management of Patients with ST-T Segment Elevation Myocardial Infarction.

The ongoing coronavirus disease 2019 (COVID-19) has caused a global health crisis. This prospective, observational, single-centre, cohort study investigated the influence of the second wave of the pandemic on the treatment of ST-segment elevation myocardial infarction (STEMI) patients admitted to the largest tertiary centre in Nicosia, Cyprus. We measured onset-to-door (O2D) time, door-to-balloon (D2B) time, onset-to-balloon (O2B) time, and 30-day mortality for 250 consecutive patients who presented directly or were transferred to Nicosia General Hospital from 1 January 2021, to 31 December 2021, during the second wave of the pandemic in Cyprus. We compared a control group of patients with similar clinical characteristics admitted before the COVID-19 outbreak. Median O2D time was increased from 89 min to 120 min (p-value=0.094). D2B time was not increased significantly (85.5 vs. 87 min, p-value=0.137). The total ischemic time (O2B time) was increased from 173.5 min to 232.5 min, respectively (173.5 vs. 232.5, p=0.001). During the pandemic, more patients presented with cardiogenic shock (3.94 vs. 13.6, p=0.001) and with cardiac arrest (9.85 vs. 17.2, p=0.035,) while there was an increase in 30-day mortality (4.43% vs. 8.8%, p-value=0.100). Patients with STEMI during the second wave of the COVID-19 pandemic seem to have presentation delays with increased total ischaemic times, presented more commonly in cardiogenic shock or cardiac arrest, increasing 30-day mortality.

Comparison of MANTA vs ProGlide Vascular Closure Device and 30-Day Outcomes in Transfemoral Transcatheter Aortic Valve Implantation.

BACKGROUND: Vascular complications (VCs) after transfemoral transcatheter aortic valve implantation (TAVI) have an increased mortality risk, and vascular closure device (VCD) use is mandatory. The percutaneous MANTA VCD (Teleflex) is a novel collagen-based technology for closure of large-bore arteriotomies. We compared the MANTA VCD with the suture-based ProGlide VCD (Abbott Vascular). METHODS: A retrospective review was performed on all consecutive patients who underwent transfemoral TAVI in our center from January 1, 2015, to February 28, 2021, and 30-day outcomes were recorded. Major adverse cardiovascular events (MACE) were cardiac death, disabling stroke, and/or major VCs. Access site-related VCs were VCs related to the access site vessel from which the transcatheter valve was introduced and advanced. RESULTS: The MANTA VCD was used in 99 patients and the ProGlide in 224. There was 4.0% MACE in the MANTA group and 4.9% in the ProGlide group (P = .999). Overall VCs were 10.1% vs 7.6%, major VCs were 3.0% vs 2.2%, and minor VCs 7.1% vs 5.4%(P = .753). Access site-related VCs were 5.1% vs 5.8% in the (P = .999), and periprocedural vascular surgical intervention was needed in 6.1% of the MANTA group vs 2.2% of the ProGlide group (P = .099). CONCLUSION: There was no significant difference in MACE, mortality, cardiovascular mortality, VCs, access site-related VCs, periprocedural vascular surgical interventions, bleeding, or transfusion rate between the 2 groups. The MANTA VCD group had more periprocedural vascular surgical interventions which did not reach statistical significance.

Syncope in a Patient With Giant Left Main Coronary Aneurysm: Is There a Link With Ventricular Arrhythmias?

Giant aneurysm of the left main coronary artery is exceedingly rare and accounts for less than 2% of patients undergoing coronary angiography. The etiology varies depending on the patient's age and geographic area, but half are of atherosclerotic origin. In most cases, coronary aneurysms are asymptomatic, however, symptomatic patients present with symptoms characteristic of coronary artery disease such as chest pain (angina pectoris), myocardial infarction, congestive heart failure, and even sudden death. Coronary angiography is considered the gold standard tool to determine the presence or absence of coronary artery disease, and if present, its size and location. Herein, we report a case of giant aneurysm of the left main coronary artery presenting as syncope and documented nonsustained ventricular tachycardia.

A Case of Right Ventricular Thrombus in a Patient With Recent COVID-19 Infection.

Coronavirus disease 2019 (COVID-19) is a viral respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The respiratory system is the main target of the virus; however, apart from lung disease, a relatively large proportion of patients develop thrombosis as well. We present the case of a 19-year-old male who was admitted after contracting community-acquired right-sided pneumonia. The patient had a history of COVID-19 infection four weeks before admission. The echocardiographic assessment revealed a 16 x 6-mm right ventricular (RV) thrombus. He underwent a cardiovascular magnetic resonance (CMR) study, which confirmed the findings. After ruling out the most common causes of hypercoagulability, COVID-19 was judged to be the cause of the thrombus. The patient was treated with warfarin. Follow-up imaging with echocardiography and CMR six months later revealed complete resolution of the thrombus. Hypercoagulability is a major complication of COVID-19 and in situ thrombosis can occur both in the arterial and venous circulation. The recognition of intracardiac thrombi even in low-risk patients with a history of COVID-19 infection and the immediate initiation of antithrombotic treatment to minimize the risk of embolization is of paramount importance. Advanced imaging techniques are often required to establish the diagnosis of this condition.

Prognostic role of inflammatory cytokines and novel adipokines in acute myocardial infarction: An updated and comprehensive review.

Acute myocardial infarction (AMI) is one of the major causes of morbidity and mortality worldwide. The inflammation response during and after AMI is common and seems to play a key role in the peri-AMI period, related with ischaemia-reperfusion injury, adverse cardiac remodelling, infarct size and poor prognosis. In this article, we provide an updated and comprehensive overview of the most important cytokines and adipokines involved in the complex pathophysiology mechanisms in AMI, summarizing their prognostic role post-AMI. Data so far support that elevated levels of the major proinflammatory cytokines TNFα, IL-6 and IL-1 and the adipokines adiponectin, visfatin and resistin, are linked to high mortality and morbidity. In contrary, there is evidence that anti-inflammatory cytokines and adipokines as IL-10, omentin-1 and ghrelin can suppress the AMI-induced inflammatory response and are correlated with better prognosis. Mixed data make unclear the role of the novel adipokines leptin and apelin. After all, imbalance of pro-inflammatory and anti-inflammatory cytokines may result in worst AMI prognosis. The incorporation of these inflammation biomarkers in established prognostic models could further improve their prognostic power improving overall the management of AMI patients.

Saphenous Vein Graft Aneurysm after Drug-Eluting Stent Implantation: Treatment by Covered Stent.

Saphenous vein graft aneurysms (SVGAs) occur as a rare complication of coronary artery bypass graft but increases the risk of morbidity and mortality. Atherosclerosis is considered to be the most common cause of saphenous vein graft aneurysms. Other etiologies include infections, varicosities of vein grafts, and surgical technical issues. These aneurysms usually present as an incidental finding of a mediastinal or cardiac mass on chest radiograph. Symptomatic aneurysms may present with a wide variety of clinical manifestations such as chest pain/angina, shortness of breath, and myocardial infarction. Treatment options of SVG aneurysms include surgery, percutaneous intervention (including vascular plugs, covered stents, and embolization coils), and conservative management. Herein, we describe a case of a saphenous vein graft aneurysm that developed after percutaneous intervention, which has never been described, to our knowledge, in the previous literature. The aneurysm was treated with polytetrafluoroethylene covered stent implantation.

Current Trends in TAVI Access.

The optimal approach for Transcatheter aortic valve implantation (TAVI) is the transfemoral access but alternative TAVI approaches offer the possibility of valve replacement in patients who are not eligible to the transfemoral route. This review paper intends to compare the current available alternative approaches for TAVI in terms of their safety and efficacy, based on the current literature. The transapical, transaortic, transsubclavian, transcarotid, transcaval and suprasternal approaches have been analyzed. The choice of the alternative approach dependents on local Heart Team expertise, patient specific characteristics, access specific characteristics and the need or not for general anesthesia. More studies are needed to investigate the impact of each individual approach on long-term outcomes.

Outcomes of transfemoral transcatheter aortic valve implantation (TAVI) and predictors of thirty-day major adverse cardiovascular events (MACE) and one-year mortality.

OBJECTIVE: TAVI is more frequently used to treat aortic stenosis with the mandate to have a low as possible rate of adverse events. We present our 30-day outcomes and one-year mortality and examine the factors associated with them. METHODS: A prospective evaluation was performed of all patients who underwent transfemoral TAVI in Nicosia General Hospital from January 2015 until March 2020. MACE were defined as cardiac death, disabling stroke, and/or major vascular complications (VC). Multiple logistic and Cox regression analyses were used to identify the factors associated with 30-day MACE and one-year mortality, respectively. RESULTS: A total of 235 TAVI procedures were performed (178 balloon-expandable, 57 self-expandable). Thirty-day outcomes were MACE: 4.3%, cardiovascular death: 2.1%, disabling stroke: 1.3%, major VC: 1.7%, and contrast induced nephropathy (CIN): 4.3%. There was a rate of 6.2% new pacemaker implantations and 0.9% of more than mild aortic valve regurgitation (AR) at 30 days. Mortality at one year was 15.1%. The balloon-expandable valves appear to have less new pacemakers, less mild AR, lower contrast volume used, and less days of hospitalization, while the self-expandable valves have lower post-procedural gradients. Low hemoglobulin, history of atrial fibrillation (AF), and lower BMI were predictors of 30-day MACE. Serum creatinine >2 mg/dL, history of AF, RVSP >60 mmHg and major VC are predictors of one-year mortality. CONCLUSION: We have shown excellent 30-day results with low incidence of adverse events for both the balloon-expandable and self-expandable valves. Clinical factors are the main predictors of both 30-day MACE and one-year mortality; major VC is a strong predictor of one-year mortality.

Syncope in a hypertrophic heart at a wedding party: can happiness break a thick heart? Takotsubo cardiomyopathy complicated with left ventricular outflow tract obstruction in a hypertrophic heart.

A 70-year-old woman with known history of hypertension presented because of a syncopal episode during dinner at a wedding party, followed by chest pain. On physical examination a systolic murmur was noted, and her electrocardiogram showed ST segment elevation in anterior leads. She had elevated troponin levels while echocardiography showed a hypertrophic interventricular septum with dyskinetic apex and left ventricular outflow (LVOT) obstruction. Emergency coronary angiography excluded obstructive coronary artery disease and confirmed the presence of LVOT obstruction with a gradient of 90 mm Hg. A left ventriculography showed hypercontractility of the basal and mid segments with apical wall dyskinesia indicating Takotsubo cardiomyopathy. Patient was discharged after 6 days of hospitalization with normalization of left ventricular function and regression of the LVOT obstruction. This is an interesting case of Takotsubo cardiomyopathy complicated with severe LVOT obstruction in a patient with hypertensive heart disease and a sigmoid septum hypertrophy.

Catheter closure of atrial septal defects using the Cocoon septal occluder: preliminary results of a European multicenter study.

Despite its simplicity, device closure of atrial septal defects is still associated with rare but potentially lethal complications. In this prospective non-randomized multicenter study we investigated the safety and efficacy of the Cocoon septal occluder (CSO) for closure of atrial septal defects (ASDs) in 92 patients. Median age of the patients was 10.5 years (range 3-61 years) and median weight was 25 kg (range 13-65 kg). The device is an improved new generation double disc design made of Nitinol wire mesh that is coated with platinum using NanoFusion technology. The discs are connected by a waist with diameter ranging from 6mm to 40 mm with 2mm increments. All patients completed a 3-month follow-up. Mean ASD diameter was 21 ± 7 mm (range 10-35 mm), while the mean device diameter was 24 ± 8 mm (range 14-40 mm). The CSO was permanently implanted in all 92 patients. Complete echocardiographic closure of the defect immediately after the procedure or at the one month follow-up, was observed in all 92 patients (100%). No device-related complications were observed during the procedure or at short-term follow-up (range 3-12 months). Our preliminary results indicate that CSO is a promising device for transcatheter closure of ASDs. Further studies are required to document its efficacy, safety and long-term results in a larger patient population.