ERRATUM: Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Relation between cardiac magnetic resonance-assessed interstitial fibrosis and diastolic dysfunction in heart failure due to dilated cardiomyopathy.

Background: Dilated cardiomyopathy (DCM) is distinguished by left ventricle (LV) dilation accompanied by systolic dysfunction. However, some studies suggested also a high prevalence of LV diastolic dysfunction (LVDD), similar to a general cohort of heart failure (HF) with reduced ejection fraction (LVEF). The bulk of evidence, mostly arising from basic studies, suggests a causative link between cardiac fibrosis (CF) and LVDD. However, still, there remains a scarcity of data on LVDD and CF. Therefore, the aim of the study was to investigate the association between CF and LVDD in DCM patients. Methods: The study population was composed of 102 DCM patients. Replacement CF was evaluated qualitatively (late gadolinium enhancement - LGE) and quantitively (LGE extent); interstitial cardiac fibrosis was assessed via extracellular volume (ECV). Based on echocardiography patients were divided into normal and elevated left atrial pressure (nLAP, eLAP) groups. Results: 42 % of patients had eLAP. They displayed higher troponin and NT-proBNP. Both groups did not differ in terms of LGE presence and extent; however, eLAP patients had larger ECV: 30.1 ± 5.6 % vs. 27.8 ± 3.9 %, p = 0.03. Moreover, ECV itself was found to be an independent predictor of LVDD (OR = 0.901; 95 %CI 0.810-0.999; p = 0.047; normalised for LVEF and RVOT diameter). Conclusions: More than two-in-five DCM patients had at least moderate LVDD. The mere presence or extent of replacement cardiac fibrosis is similar in patients with nLAP and eLAP. On the other hand, interstitial cardiac fibrosis is more pronounced in those with a higher grade of LVDD. ECV was found to be an independent predictor of LVDD in DCM.

Transthyretin amyloid cardiomyopathy in patients with unexplained increased left ventricular wall thickness.

Amyloid cardiomyopathy (CA) was previously considered a rare disease; however, rapid advancements in imaging modalities have led to an increased frequency of its diagnosis. The aim of this prospective study was to assess the prevalence and clinical phenotype of transthyretin amyloidosis (ATTR) cardiomyopathy in patients exhibiting unexplained increased left ventricular (LV) wall thickness. From 2020 to 2022, we enrolled 100 consecutive adults with unexplained increased LV wall thickness in the study. The analysis included clinical data, electrocardiography, transthoracic echocardiography, single-photon emission computed tomography/computed tomography with 3,3-disphono-1,2-propanodicarboxylic acid, genetic testing. Overall, 18% of patients were diagnosed with CA, comprising 5% with light-chain amyloidosis, and 12% with ATTR. To evaluate associations with the ATTR diagnosis, a LOGIT model and multivariate analysis were applied. Notably, age, polyneuropathy, gastropathy, carpal tunnel syndrome, lumbar spine stenosis, low voltage, ventricular arrhythmia, LV mass, LV ejection fraction, global longitudinal strain (GLS), E/A, E/E', right ventricle (RV) thickness, right atrium area, RV VTI, TAPSE, apical sparing, ground glass appearance of myocardium, thickening of interatrial septum, thickening of valves, and the "5-5-5" sign were found to be significantly associated with ATTR (p < 0.05). The best predictive model for ATTR diagnoses exhibited an area under the curve of 0.99, including LV mass, GLS and RV thickness. This study, conducted at a cardiology referral center, revealed that a very considerable proportion of patients with unexplained increased LV wall thickness may suffer from underlying CA. Moreover, the presence of ATTR should be considered in patients with increased LV mass accompanied by reduced GLS and RV thickening.

Genetic testing for inherited cardiovascular diseases. A position statement of the Polish Cardiac Society endorsed by Polish Society of Human Genetics and Cardiovascular Patient Communities.

According to the latest guidelines of European and American medical societies, genetic testing (GT) is essential in cardiovascular diseases for establishing diagnosis, predicting prognosis, enabling initiation of disease-modifying therapy, and preventing sudden cardiac death. The GT result may be relevant for cascade GT in the patient's relatives, for planning his/her profession and physical activity, and for procreative counseling. This position statement has been prepared due to the scarcity of GT in cardiovascular diseases in Poland and the need to expand its availability. We give a concise description of the genetic background of cardiomyopathies, channelopathies, aortopathies, familial hypercholesterolemia, pheochromocytomas, and paragangliomas. The article discusses various aspects of GT in specific populations, such as children or athletes, and also presents prenatal genetic diagnostics. We propose recommendations for GT and counselling, which take into account Polish needs and capabilities. We give an outline of legal regulations, good clinical practice in GT with respect for patient rights, the role of cardiologists and clinical geneticists in GT planning and post-test counseling, and the requirements for laboratories performing genetic tests. The Polish Cardiac Society and Polish Society of Human Genetics experts speak with one voice with cardiovascular patient communities to underline the need for a law on GT and increasing the availability of GT for cardiovascular patients.

Temporal progression of replacement and interstitial fibrosis in optimally managed dilated cardiomyopathy patients: A prospective study.

BACKGROUND: To prospectively examine the dynamic evolution of fibrotic processes within a one-year in patients with dilated cardiomyopathy (DCM). METHODS: Between May 2019 and September 2020, 102 DCM patients (mean age 45.2 ± 11.8 years, EF 29.9 ± 11.6%) underwent cardiac magnetic resonance (CMR-1). After 13.9 ± 2.9 months, 92 of these patients underwent a follow-up CMR (CMR-2). Replacement fibrosis was assessed via late gadolinium enhancement (LGE), quantified in terms of LGE mass and extent. Interstitial fibrosis was evaluated via T1-mapping and expressed as extracellular volume fraction (ECV). This data, along with left ventricular (LV) mass, facilitated the calculation of LV matrix and cellular volumes. RESULTS: At CMR-1, LGE was present in 45 patients (48.9%), whereas at CMR-2 LGE was detected in 46 (50%) (p = 0.88). Although LGE mass remained stable, LGE extent increased from 2.18 ± 4.1% to 2.7 ± 4.6% (p < 0.01). Conversely, ECV remained unchanged [27.7% (25.5-31.3) vs. 26.7% (24.5-29.9); p = 0.19]; however, LV matrix and cell volumes exhibited a noteworthy regression. During a subsequent follow-up of 19.2 ± 9 months (spanning from CMR-2 to April 30th, 2023), the composite primary outcome (all-cause mortality, HTX, LVAD or heart failure worsening) was evident in 18 patients. Only the LV matrix volume index at follow-up was an independent predictor of outcome (OR 1.094; 95%CI 1.004-1.192; p < 0.05). CONCLUSIONS: In optimally managed DCM patients, both replacement and interstitial fibrosis remained stable over the course of one year. In contrast, LV matrix and cell volumes displayed significant regression. LV matrix volume index at 12-month follow-up was found to be an independent predictor of outcome in DCM.

Identification and therapy for patients with heart failure with preserved ejection fraction: An expert opinion of the Heart Failure Association of the Polish Cardiac Society.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) may be challenging owing to the heterogeneous clinical presentation and comorbidities in this population of patients, along with the limited availability of standard diagnostic tools, including natriuretic peptide tests and functional testing. This expert opinion summarizes the current state of knowledge on the identification and therapy for patients with HFpEF based on recent European and American recommendations. This expert opinion aims to aid clinicians in HFpEF management.

Diagnosis and treatment of transthyretin amyloidosis cardiomyopathy: A position statement of the Polish Cardiac Society.

Considering the rare incidence of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in Poland, patients encounter difficulties at the stages of diagnosis and treatment. For successful diagnosis, it is vital to raise the suspicion of ATTR-CM, that is, to identify typical clinical scenarios such as heart failure with preserved ejection fraction or the red flags of amyloidosis. In most cases, it is possible to establish the diagnosis on the basis of noninvasive tests. This article presents the recommended diagnostic algorithms including laboratory workup, imaging tests (in particular, isotope scanning), and genetic tests. Since ATTR-CM should be differentiated from light chain amyloidosis, we also discuss aspects related to hematological manifestations and invasive diagnosis. We describe neurological signs and symptoms in patients with amyloidosis and present therapeutic options, including the causative treatment of ATTR-CM with the only currently approved drug, tafamidis. We also discuss drugs that are being assessed in ongoing clinical trials. We outline differences in the symptomatic treatment of heart failure in ATTR-CM and recommendations for nonpharmacological treatment and monitoring of the disease. Finally, we underline the need for providing access to the causative treatment with tafamidis as part of a drug program, as in other rare diseases, so that patients with ATTR-CM can be treated according to the European Society of Cardiology guidelines on heart failure and cardiomyopathy.

Link between fibrosis-specific biomarkers and interstitial fibrosis in hypertrophic cardiomyopathy.

BACKGROUND: Cardiac fibrosis is a hallmark of hypertrophic cardiomyopathy (HCM) and has confirmed unfavorable clinical significance. Replacement fibrosis is better known and has already been studied on a larger scale, whereas interstitial fibrosis is less explored. AIMS: We aimed to analyze the relationship between serum biomarkers and interstitial fibrosis, as assessed with cardiac magnetic resonance (CMR) in HCM patients. METHODS: We performed 3T CMR scans in 50 HCM patients to assess interstitial fibrosis as expressed by extracellular volume (ECV). In all patients, we determined levels of serum cardiac-specific (troponin T [TnT], N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) and fibrosis-specific (procollagen I C-terminal propeptide, procollagen III N-terminal propeptide, transforming growth factor ß1, galectin-3) biomarkers. Patients were divided based on their median value of ECV. RESULTS: The final study population included 49 patients. The median value of ECV in our cohort was 28.1%. Patients stratified according to median ECV differed in terms of several variables: body mass index, late gadolinium extent, NT-proBNP, and galectin-3 levels (all P <0.05). Cardiac biomarkers (TnT and NT-proBNP) and galectin-3 were significantly correlated with ECV (rS = 0.34; P = 0.02; rS = 0.39; P = 0.006; rS = 0.43; P = 0.002, respectively). Galectin-3 and body mass index were found to be independent predictors of ECV (odds ratio [OR], 2.29 [1.07-4.91]; P = 0.03; OR, 0.81 [0.68-0.97]; P = 0.02, respectively). CONCLUSIONS: Galectin-3 was an independent predictor of interstitial fibrosis in HCM patients expressed as elevated ECV values. The other measured fibrosis-specific biomarkers were not useful in detecting interstitial fibrosis in HCM. In addition, there was a positive correlation between classical cardiac biomarkers and interstitial fibrosis in HCM patients.

Expert opinion of the Heart Failure Association of the Polish Society of Cardiology, the College of Family Physicians in Poland, and the Polish Society of Family Medicine on the peri discharge management of patients with heart failure.

Despite advances in the treatment of heart failure (HF), the rate of hospitalisation for exacerbations of the disease remains high. One of the underlying reasons is that recommended guidelines for the management of HF are still too rarely followed in daily practice. Disease exacerbation requiring inpatient treatment is always afactor that worsens the prognosis, and thus signals disease progression. This is also akey moment when therapy should be modified for HF exacerbation, or initiated in the case of newly diagnosed disease. Inpatient treatment and the peri­discharge period is the time when the aetiology and mechanism of HF decompensation should be established. Therapy should be individualised based on aetiology, HF phenotype, and comorbidities; it should take into account the possibilities of modern treatment. According to the recommendations of the European Society of Cardiology (ESC), patients with HF should receive multidisciplinary management. Cooperation between the various members of the multidisciplinary team taking care of patients with HF improves the efficiency and quality of treatment. This document expands and details the information on the peri­discharge management of HF contained in the 2021 ESC guidelines and the 2022 American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) guidelines.

Comparison of Clinical Course and Outcomes between Dilated and Hypokinetic Non-Dilated Cardiomyopathy.

BACKGROUND: By definition, dilated cardiomyopathy (DCM) is characterized by enlargement of the left ventricular (LV) cavity, and systolic dysfunction. However, in 2016 ESC introduced a new clinical entity - hypokinetic non-dilated cardiomyopathy (HNDC). HNDC is defined as LV systolic dysfunction without LV dilatation. However, the diagnosis of HNDC has so far rarely been made by a cardiologist, and it is unknown whether "classic" DCM differs from HNDC in terms of clinical course and outcomes. OBJECTIVES: Comparison of heart failure profiles and outcomes between patients with "classic" dilated (DCM) and HNDCs. METHOD: We retrospectively analysed 785 DCM patients, defined as impaired left ventricle (LV) systolic function (ejection fraction [LVEF] <45%) in the absence of coronary artery disease, valve disease, congenital heart disease, and severe arterial hypertension. "Classic" DCM was diagnosed when LV dilatation was present (LV end-diastolic diameter >52 mm/58 mm in women/men); otherwise, HNDC was diagnosed. After 47 ± 31 months, the all-cause mortality and composite endpoint (all-cause mortality, heart transplant - HTX, left ventricle assist device implantation - LVAD) were assessed. RESULTS: There were 617 (79%) patients with LV dilatation. Patients with "classic" DCM differed from HNDC in terms of clinically relevant parameters [hypertension (47% vs. 64%, p = 0.008), ventricular tachyarrhythmias (29% vs. 15%, p = 0.007), NYHA class (2.5 ± 0.9 vs. 2.2 ± 0.8, p = 0.003)], had lower cholesterol (LDL: 2.9 ± 1.0 vs. 3.2 ± 1.1 mmol/L, p = 0.049), and higher N-terminal pro-brain natriuretic peptide (3,351 ± 5,415 vs. 2,563 ± 8584 pg/mL, p = 0.0001) and required higher diuretics dosages (57.8 ± 89.5 vs. 33.7 ± 48.7 mg/day, p ≤ 0.0001). All of their chambers were larger (LVEDd: 68.3 ± 4.5 vs. 52.7 ± 3.5 mm, p < 0.0001) and they had lower LVEF (25.2 ± 9.4 vs. 36.6 ± 11.7%, p < 0.0001). During the follow-up, there were 145 (18%) composite endpoints ("classic" DCM vs. HNDC: 122 [20%] vs. 26 [18%], p = 0.22): deaths (97 [16%] vs. 24 [14%], p = 0.67), HTX (17 [4%] vs. 4 [4%], p = 0.97) and LVAD (19 [5%] vs. 0 [0%], p = 0.03). Both groups did not differ in terms of all-cause mortality (p = 0.70), cardiovascular (CV) mortality (p = 0.37) and composite endpoint (p = 0.26). CONCLUSIONS: LV dilatation was absent in more than one-fifth of DCM patients. HNDC patients had less severe heart failure symptoms, less advanced cardiac remodelling, and required lower diuretics dosages. On the other hand, "classic" DCM and HNDC patients did not differ in terms of all-cause mortality, CV mortality, and composite endpoint.

Advances in Molecular Imaging in Infective Endocarditis.

Infective endocarditis (IE) is a growing epidemiological challenge. Appropriate diagnosis remains difficult due to heterogenous etiopathogenesis and clinical presentation. The disease may be followed by increased mortality and numerous diverse complications. Developing molecular imaging modalities may provide additional insights into ongoing infection and support an accurate diagnosis. We present the current evidence for the diagnostic performance and indications for utilization in current guidelines of the hybrid modalities: single photon emission tomography with technetium99m-hexamethylpropyleneamine oxime-labeled autologous leukocytes (99mTc-HMPAO-SPECT/CT) along with positron emission tomography with fluorodeoxyglucose (18F-FDG PET/CT). The role of molecular imaging in IE diagnostic work-up has been constantly growing due to technical improvements and the increasing evidence supporting its added diagnostic and prognostic value. The various underlying molecular processes of 99mTc-HMPAO-SPECT/CT as well as 18F-FDG PET/CT translate to different imaging properties, which should be considered in clinical practice. Both techniques provide additional diagnostic value in the assessment of patients at risk of IE. Nuclear imaging should be considered in the IE diagnostic algorithm, not only for the insights gained into ongoing infection at a molecular level, but also for the determination of the optimal clinical therapeutic strategies.

To what extent does prior antimicrobial therapy affect the diagnostic performance of radiolabeled leukocyte scintigraphy in infective endocarditis?

AIMS: This prospective, single-center study sought to assess to what extent there is interference between the hybrid technique of single-photon emission tomography-computed tomography with technetium99m-hexamethylpropyleneamine oxime-labeled leukocytes (99mTc-HMPAO-SPECT/CT) and antimicrobial therapy in patients with infective endocarditis (IE). METHODS AND RESULTS: During the years 2015-2019, we enrolled 205 consecutive adults with suspected IE, all underwent 99mTc-HMPAO-SPECT/CT. The study population was divided into those who had received antimicrobial therapy up to 30 days prior to 99mTc-HMPAO-SPECT/CT (group 1, n = 96) and those who had not (group 2, n = 109). Patients were prospectively observed for 12 ± 10 months. Group 1 presented higher positive predictive values (91.89% vs. 60.00%, = 0.001), and decreased negative predictive values (77.97% vs. 90.54%, P = 0.04). Patients treated with antimicrobial therapy displayed false-negative 99mTc-HMPAO-SPECT/CT results more often [odds ratio (OR), 4.63; 95% confidence interval (CI), 1.41-15.23, P = .01], particularly when intravenous (OR 5.37; 95% CI 1.73-16.62, P = .004), definite (OR 9.43; 95% CI 2.65-33.51, P = .001), and combination antibiotic regimens (OR 8.1; 95% CI 2.57-25.64, P = .001) had been administered. CONCLUSION: Prior antibiotic therapy affects 99mTc-HMPAO-SPECT/CT diagnostic properties. Patients treated with antimicrobial therapy display false-negative 99mTc-HMPAO-SPECT/CT results more often, especially if intravenous, definite, or combination regimens are administered.

How does age affect outcomes after left ventricular assist device implantation: results from the PCHF-VAD registry.

AIMS: Use of left ventricular assist devices (LVADs) in older patients has increased, and assessing outcomes in older LVAD recipients is important. Therefore, this study aimed to investigate associations between age and outcomes after continuous-flow LVAD (cf-LVAD) implantation. METHODS AND RESULTS: Cf-LVAD patients from the multicentre European PCHF-VAD registry were included and categorized into those <50, 50-64, and ≥65 years old. The primary endpoint was all-cause mortality. Among secondary outcomes were heart failure (HF) hospitalizations, right ventricular (RV) failure, haemocompatibility score, bleeding events, non-fatal thromboembolic events, and device-related infections. Of 562 patients, 184 (32.7%) were <50, 305 (54.3%) were aged 50-64, whereas 73 (13.0%) were ≥65 years old. Median follow-up was 1.1 years. Patients in the oldest age group were significantly more often designated as destination therapy (DT) candidates (61%). A 10 year increase in age was associated with a significantly higher risk of mortality (hazard ratio [HR] 1.34, 95% confidence interval [CI] [1.15-1.57]), intracranial bleeding (HR 1.49, 95% CI [1.10-2.02]), and non-intracranial bleeding (HR 1.30, 95% CI [1.09-1.56]), which was confirmed by a higher mean haemocompatibility score (1.37 vs. 0.77, oldest vs. youngest groups, respectively, P = 0.033). Older patients suffered from less device-related infections requiring systemic antibiotics. No age-related differences were observed in HF-related hospitalizations, ventricular arrhythmias, pump thrombosis, non-fatal thromboembolic events, or RV failure. CONCLUSIONS: In the PCHF-VAD registry, higher age was associated with increased risk of mortality, and especially with increased risk of major bleeding, which is particularly relevant for the DT population. The risks of HF hospitalizations, pump thrombosis, ventricular arrhythmia, or RV failure were comparable. Strikingly, older patients had less device-related infections.

Sex-related differences in left ventricular assist device utilization and outcomes: results from the PCHF-VAD registry.

AIMS: Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly confined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization and outcomes in a contemporary European LVAD cohort. METHODS AND RESULTS: This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients. The primary outcome was all-cause mortality. Secondary outcomes included ventricular arrhythmias, right ventricular failure, bleeding, thromboembolism, and the haemocompatibility score. Multivariable Cox regression models were used to assess associations between sex and outcomes. Overall, 457 men (81%) and 105 women (19%) were analysed. At LVAD implant, women were more often in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2 (55% vs. 41%, P = 0.009) and more often required temporary mechanical circulatory support (39% vs. 23%, P = 0.001). Mean age was comparable (52.1 vs. 53.4 years, P = 0.33), and median follow-up duration was 344 [range 147-823] days for women and 435 [range 190-816] days for men (P = 0.40). No significant sex-related differences were found in all-cause mortality (hazard ratio [HR] 0.79 for female vs. male sex, 95% confidence interval [CI] [0.50-1.27]). Female LVAD patients had a lower risk of ventricular arrhythmias (HR 0.56, 95% CI [0.33-0.95]) but more often experienced right ventricular failure. No significant sex-related differences were found in other outcomes. CONCLUSIONS: In this contemporary European cohort of LVAD patients, far fewer women than men underwent LVAD implantation despite similar clinical outcomes. This is important as the proportion of female LVAD patients (19%) was lower than the proportion of females with advanced HF as reported in previous studies, suggesting underutilization. Also, female patients were remarkably more often in INTERMACS profile 1 or 2, suggesting later referral for LVAD therapy. Additional research in female patients is warranted.