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.

Left ventricular thrombus in a patient with recurrent ischemic stroke events-The role of echocardiography.

Key Clinical Message: Cardiac ultrasound is recommended in investigating ischemic stroke events. There is increasing evidence that direct oral anticoagulants can be safely used instead of vitamin K antagonists in the setting of left ventricular thrombus. Abstract: Cardioembolic stroke is responsible for an increasing number of ischemic strokes. Compared to other causes of stroke, cardioembolic strokes affect a larger brain area. Left ventricular (LV) thrombi account for up to 10% of cardioembolic strokes. It is essential to identify patients at high risk of LV thrombus formation, such as patients with a history of myocardial infarction, patients with reduced ejection fraction, or patients with cardiomyopathies. We present a patient with an ischemic stroke, and the cardiac ultrasound revealed a reduced ejection fraction and the presence of LV thrombus at the apex. The patient had no prior history of cardiovascular diseases. Even in a resource-limited setting, cardiac ultrasound is recommended to investigate stroke or transient ischemic attack events, especially in patients with a prior history of myocardial infarction. Although patients with LV thrombus should be treated with oral anticoagulants for at least 3 months, the role of direct oral anticoagulants and the optimal period of anticoagulation in this setting needs further investigation.

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.

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.

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.

Cardiovascular Outcomes Following Rotational Atherectomy: A UK Multicentre Experience.

OBJECTIVES: To identify factors associated with outcomes following rotational atherectomy (RA). BACKGROUND: RA is an effective way to mechanically modify heavily calcified lesions before stenting; however its outcomes are not well defined. METHODS AND RESULTS: Retrospective evaluation of all patients who underwent RA in three large UK centers (Leeds General Infirmary (LGI), Royal Infirmary of Edinburgh (RIE) and University Hospital of North Staffordshire (UHNS)) from March 2005 to January 2013. Five hundred and eighteen patients had RA with median follow-up period of 22 months. About 68.3% were male, 28.7% had DM and 34.6% were treated because of ACS. Stents were deployed in 97.3% of the patients while 30.7% of the procedures were performed transradially. Maximum burr was ≤1.75 mm in 85.5% and the mean SYNTAX score was 19.5 ± 11.6. Peri-procedural complications occurred in 6.4% and vascular access complications in 1.9%. Outcomes in the follow-up period were: MACE 17.8%, cardiac death 7.1%, MI 11.7%, TVR 7.5%, all-cause death 13.7%, definite stent thrombosis (ST) 1.4% and stroke 2.9%. Patients with intermediate and high SYNTAX scores were more likely to suffer MACE, cardiac death, MI, all-cause death and ST. Patients with a SYNTAX score >32 were also more likely to have a peri-procedural complication. Multiple logistic regression analysis showed that the presence of PVD (P = 0.026, OR = 2.0), DM (P = 0.008, OR = 2.1), ACS presentation (P = 0.011, OR = 2.1) and SYNTAX score ≥23 (P = 0.02, OR = 1.9) had a significant association with MACE. CONCLUSIONS: RA is safe and effective, with high rate of procedural success and relatively low incidence of MACE. PVD, DM, ACS presentation and SYNTAX score were significant predictors for MACE. © 2016 Wiley Periodicals, Inc.

Treatment of aortic stenosis with a self-expanding transcatheter valve: the International Multi-centre ADVANCE Study.

AIM: Transcatheter aortic valve implantation has become an alternative to surgery in higher risk patients with symptomatic aortic stenosis. The aim of the ADVANCE study was to evaluate outcomes following implantation of a self-expanding transcatheter aortic valve system in a fully monitored, multi-centre 'real-world' patient population in highly experienced centres. METHODS AND RESULTS: Patients with severe aortic stenosis at a higher surgical risk in whom implantation of the CoreValve System was decided by the Heart Team were included. Endpoints were a composite of major adverse cardiovascular and cerebrovascular events (MACCE; all-cause mortality, myocardial infarction, stroke, or reintervention) and mortality at 30 days and 1 year. Endpoint-related events were independently adjudicated based on Valve Academic Research Consortium definitions. A total of 1015 patients [mean logistic EuroSCORE 19.4 ± 12.3% [median (Q1,Q3), 16.0% (10.3, 25.3%)], age 81 ± 6 years] were enrolled. Implantation of the CoreValve System led to a significant improvement in haemodynamics and an increase in the effective aortic valve orifice area. At 30 days, the MACCE rate was 8.0% (95% CI: 6.3-9.7%), all-cause mortality was 4.5% (3.2-5.8%), cardiovascular mortality was 3.4% (2.3-4.6%), and the rate of stroke was 3.0% (2.0-4.1%). The life-threatening or disabling bleeding rate was 4.0% (2.8-6.3%). The 12-month rates of MACCE, all-cause mortality, cardiovascular mortality, and stroke were 21.2% (18.4-24.1%), 17.9% (15.2-20.5%), 11.7% (9.4-14.1%), and 4.5% (2.9-6.1%), respectively. The 12-month rates of all-cause mortality were 11.1, 16.5, and 23.6% among patients with a logistic EuroSCORE ≤10%, EuroSCORE 10-20%, and EuroSCORE >20% (P< 0.05), respectively. CONCLUSION: The ADVANCE study demonstrates the safety and effectiveness of the CoreValve System with low mortality and stroke rates in higher risk real-world patients with severe aortic stenosis.

Bivalirudin in patients undergoing primary percutaneous coronary intervention for acute ST-elevation myocardial infarction: outcomes in a large real-world population.

AIMS: Within a clinical trial population, direct thrombin inhibition using bivalirudin in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is associated with a reduction in mortality and major bleeding compared to heparin/glycoprotein IIb/IIIa receptor inhibition (GPI), but a higher incidence of acute stent thrombosis (ST), particularly in the absence of pre-procedural heparin. The safety and efficacy of bivalirudin in an all-comer, real-world primary PCI setting is unknown. METHODS AND RESULTS: 968 consecutive STEMI patients (mean age 63 years, 72% male, 42% anterior STEMI, 3.7% cardiogenic shock) undergoing primary PCI with bivalirudin as the recommended anticoagulation, and with heparin/GPI (abciximab) as an alternative, were prospectively followed. Bivalirudin was administered as a bolus, high-dose procedural infusion and, unlike the HORIZONS-AMI trial, as a low-dose infusion for four hours post-PCI. Additional heparin was not routinely given. Mortality, major adverse cardiovascular events (MACE), major bleeding and ST were assessed at 30 days. Initial antithrombotic therapy was bivalirudin in 885 patients (91%), of whom 123 (13.9%) received additional antithrombin therapy, and 114 (11.8%) "bail-out" GPI. Outcomes for bivalirudin-treated patients were; mortality 5.2%, MACE 7.5%, major bleeding 3.8%. The incidence of acute ST was 1.0%, including in the absence of additional heparin (1.2%). Most cases of acute ST (7/9) occurred in the first four hours post-PCI. There was no significant difference in outcomes between patients treated with bivalirudin versus heparin/GPI. CONCLUSIONS: Routine use of bivalirudin in a real-world primary PCI population was associated with good 30-day outcomes. Acute stent thrombosis was infrequent, even without additional heparin. A continued low-dose infusion of bivalirudin did not appear to offer protection against very early stent thrombosis.

Homocysteine levels and MTHFR polymorphisms in young patients with acute myocardial infarction: a case control study.

INTRODUCTION: Increased levels of homocysteine are known to be associated with coronary artery disease (CAD). The most common form of genetic hyperhomocysteinemia results from MTHFR polymorphisms. To examine the role of homocysteine levels and MTHFR polymorphisms in premature CAD and acute myocardial infarction (MI) in the Cypriot population, a case control study was performed in Nicosia General Hospital. METHODS: Sixty-three male patients less than 50 years old who presented with MI in Nicosia General Hospital were compared with 54 controls without CAD. Fasting homocysteine and lipids were tested within 24 hrs from admission, while MTHFR C677T and A1298C polymorphisms were also tested. RESULTS: Mean homocysteine levels were 14.5 mol/L in patients and 12.3 mol/L in controls (p=0.017). Mutant homozygous MTHFR C677T was present in 17.7% of the patients and 19.2% of the controls (p=0.838), while mutant homozygous MTHFR A1298C was found in 16.1% of patients and 13.5% of controls (p=0.690). Mean homocysteine levels were 12.6 mol/L in patients with single-vessel CAD and 15.5 mol/L in patients with multi-vessel CAD (p=0.025). Lower HDL appeared to be associated with higher levels of homocysteine with an odds ratio of 0.901, indicating that for each unit increase in HDL, the expected odds of having high homocysteine levels decreased by approximately 10%. CONCLUSIONS: Higher levels of homocysteine are associated with acute MI and multi-vessel disease in Cypriot patients under the age of 50. The existence and extent of disease are not associated with MTHFR polymorphisms. Lower HDL is associated with higher levels of homocysteine.

A penetrating heart injury resulting in ventricular septal defect.

Penetrating heart injuries can be lethal. Here we report a case of self-inflicted cardiac injury with glass fragments by a psychiatric patient. The patient presented with cardiogenic shock and was initially treated surgically for a large pneumothorax and cardiac tamponade. A few days later she presented with dyspnoea and hypotension. An echo-Doppler study was performed and an acquired post-traumatic ventricular septal defect (VSD) with left-to-right shunt was diagnosed. The patient was transferred to theatre where the defect was successfully repaired. Post-traumatic VSD is a rare complication of penetrating heart injuries and has a tendency to present late. Follow up of such cases is recommended with repeat echocardiography.

Nicosia General Hospital cardiac arrest team: first year's practice and outcomes of in-hospital resuscitation.

INTRODUCTION: In 2007, Nicosia General Hospital implemented a resuscitation policy. 378 nurses and 120 doctors were successfully trained in advanced life support (ALS) in order to staff cardiac arrest teams. The aim of this study was to assess the frequency of cardiac arrest and resuscitation outcomes in Nicosia General Hospital and assess any associations between the survival rate and the patient's characteristics. We also aimed to evaluate the effectiveness of in-hospital resuscitation in order to detect ways of improvement. METHODS: We prospectively analyzed the data on all cardiac arrest calls in Nicosia General Hospital between January and December 2007. Data were collected using the Utstein style. RESULTS: The cardiac arrest team (CAT) was called 83 times, of which 10 were false alarms. Cardiac arrest was identified in 69 calls, while 4 calls were respiratory arrests. The patients' mean age was 70.8 years (95% CI: 66.6-75.1). In 86% the initial rhythm was asystole/pulseless electrical activity (PEA) and in 14% ventricular fibrillation/tachycardia (VF/VT). Return of spontaneous circulation was achieved in 52% of the cases. Survival to discharge was achieved in 17.8% of the patients with arrest and in 14.5% of cardiac arrests. Patients with an initial rhythm of asystole/PEA were discharged in 5% and patients with VF/VT in 70% of cases. About 36% of the patients less than 60 years old and 12% of the patients older than 60 were discharged. The CAT arrived within 1.6 minutes, first shock in VF/VT was delivered within 1.5 minutes and the first adrenaline dose in asystole/PEA was given within 2.7 minutes. CONCLUSIONS: It is more likely for our patients to survive to discharge if they are less than 60 years old, they are hospitalized in the cardiology department and the initial rhythm is VF/VT. Our outcomes are similar to survival rates in larger studies. However, points of improvement have been identified and interventions need to be made in order to improve documentation and outcomes of in-hospital arrests.

Cardiac hemangioma in the left ventricle and brief review of the literature.

Cardiac hemangiomas are very rare benign cardiac tumors. They can present at any age and clinical presentation varies according to location and size. Most common symptoms include shortness of breath, palpitations, atypical chest pain and arrhythmia. The natural history of these tumors is unpredictable. They can regress, cease growing or proliferate over time. Diagnosis is usually made with echocardiography and surgical resection is the treatment of choice. Follow-up is recommended to identify any recurrence. We report a case of a 38-year-old man who presented with fatigue and palpitations. Echocardiography revealed a mobile spherical mass within the left ventricle, whereas left ventriculography showed an intracavity-filling defect without any tumor blushing. The tumor was removed surgically through the left atrium. It was a smooth oval nodule with a pedicle that was attached to the top of a papillary muscle. Microscopy revealed the presence of numerous vessels within fibrous tissue that ranged from lobules of capillary hemangioma to large thin-walled cavernous vessels, compatible with a hemangioma of mixed capillary-cavernous type. The patient had an uneventful postoperative course and recovered quickly.

Primary cardiac lymphoma: case report and brief review of the literature.

Primary cardiac lymphoma is defined as a non-Hodgkin's lymphoma mainly located in the heart and/or the pericardium. It is rare and affects elderly men. Common manifestations are pericardial effusion and heart failure. Diagnosis is usually late and prognosis is poor. We report a case of a patient with a large primary cardiac lymphoma who presented with chest pain and negative T-waves in electrocardiogram. Transthoracic echocardiogram showed a large mass in the right atrium and right ventricle while transesophageal echocardiogram also revealed the presence of large mobile masses in the right atrium, which were considered to be thrombi. Tissue biopsy showed a high-grade B-cell diffuse lymphocytic lymphoma. The patient was treated with chemotherapy and radiation with complete remission and prolonged survival.