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.

Transthyretin cardiac amyloidosis (ATTR) is prevalent among patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis (AS). We aimed to develop and validate a risk score for predicting ATTR in this context. In the prospective multicentre GRECA-TAVI registry, 500 patients with severe AS scheduled for TAVI were screened for ATTR using technetium-99m-labeled DPD or PYP bone scintigraphy in 12 tertiary hospitals, from January 1st to December 31st, 2024. Clinical, echocardiographic, and electrocardiographic variables were recorded. A logistic regression-derived integer-based risk score was developed in a training cohort (n=350) and validated in a validation cohort (n=150). Model performance was evaluated using discrimination, calibration, and decision curve analyses. ATTR was diagnosed in 38 patients (7.6%). Five variables (age, sex, MWT, LVEF, and intracardiac device presence) formed the basis of an 8-point risk score. The score demonstrated good discrimination (AUC=0.75 training, 0.76 validation) and calibration (slope=1.15). A score ≥4 identified patients with a ∼16% ATTR prevalence compared to 2.4% in those with a score <4. This threshold captured most of the ATTR cases (73%) while recommending screening for only 36% of the cohort. Decision curve analysis showed net clinical benefit across clinically relevant thresholds (5-20%) over and above a guideline-recommended approach (based on MWT≥12mm) or a screen-all strategy. ATTR is common in patients with severe AS undergoing TAVI. A simple bedside score using routinely available variables effectively identifies those patients at risk for ATTR. Selective screening using this tool could improve diagnostic yield and resource allocation.

We present the case of a 44-year-old woman who suffered an out of hospital cardiorespiratory arrest. After six direct current shocks and 10 minutes of cardiopulmonary resuscitation she had return of spontaneous circulation and regained consciousness. Transthoracic echocardiography showed normal left ventricular ejection fraction and a mildly dilated left atrium. The mitral valve was thickened with myxomatous degeneration (Barlow’s disease) and moderate regurgitation secondary to bi-leaflet prolapse. Cardiac catheterization showed no coronary artery disease while left ventriculography revealed a mildly dilated left ventricle with preserved systolic function and high-end diastolic pressures. Cardiac MRI revealed an enlarged left ventricle with mitral valve (MV) prolapse and moderate to severe mitral regurgitation (MR). There were no features suggestive of a specific cardiomyopathy other than her valvular heart disease. The patient had an uneventful hospitalization, received an implantable cardioverter defibrillator (ICD), and eventually had MV repair surgery. A genetic investigation revealed two DNA variants, one each in the MYPN and TMPO gene, substitutions of highly conserved aminoacid residues. Family segregation could not establish unequivocally their pathogenicity although the MYPN variant represents the same residue that was shown previously to be substituted by another aminoacid. In this article we also review the literature regarding similar cases and record important data for the epidemiology of the disease and the important research that has been carried out in the identification of prognostic imaging factors and the genetic background of these patients.

Tricuspid regurgitation (TR) has historically been undertreated despite its strong association with morbidity and mortality. Surgical correction of isolated TR is not routinely performed and has shown limited survival benefit, leaving a substantial unmet need for minimally invasive therapies. Transcatheter edge-to-edge repair (T-TEER) has emerged as a promising therapeutic option for patients with symptomatic severe or greater (≥severe) TR who are unsuitable for surgery. Recent randomized trials, including the TRILUMINATE Pivotal and the Tri-FR study, and real-world registries consistently demonstrate significant improvements in TR severity, functional status, and quality of life following T-TEER. Although benefits in hard clinical endpoints such as mortality or heart failure hospitalizations remain less conclusive, growing evidence suggests potential prognostic advantage in selected patients, particularly those with preserved or mid-range right ventricular function. Anatomical suitability, RV performance, and optimized patient selection are crucial determinants of success. As ongoing large-scale trials continue to evaluate long-term outcomes, T-TEER currently occupies a therapeutic space between palliative intervention and disease-modifying therapy, providing substantial symptom relief with the potential for broader clinical benefit. This review summarizes current evidence, patient selection strategies, and perspectives on the evolving role of T-TEER in the management of severe TR.