Differences Between Two Distinct Hypertrophic Cardiac Conditions: Fabry Disease versus Hypertrophic Cardiomyopathy. / Diferenças entre Duas Condições Cardíacas Hipertróficas Distintas: Doença de Fabry Versus Cardiomiopatia Hipertrófica.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) and Fabry disease (FD) are genetically inherited diseases with left ventricular hypertrophy (LVH) phenotype characteristics that cause adverse cardiac outcomes. OBJECTIVES: To investigate the demographic, clinical, biochemical, electrocardiographic (ECG), and echocardiographic (ECHO) differences between HCM and FD. METHODS: 60 HCM and 40 FD patients were analyzed retrospectively as a subanalysis of the 'LVH-TR study' after excluding patients with atrial fibrillation, pace rhythm, bundle branch blocks, and second and third-degree atrioventricular (AV) blocks. The significance level was accepted as <0.05. RESULTS: Male gender (p=0.048) and creatinine (p=0.010) are significantly higher in favor of FD; however, ST depression (p=0.028), QT duration (p=0.041), interventricular septum thickness (IVSd) (p=0.003), posterior wall thickness (PWd) (p=0.009), moderate-severe mitral regurgitation (MR) (p=0.013), and LV mass index (LVMI) (p=0.041) are significantly higher in favor of HCM in the univariate analyses. In multivariate analysis, statistical significance only continues in creatinine (p=0.018) and QT duration (0.045). FD was positively correlated with creatinine (rho=0.287, p=0.004) and HCM was positively correlated with PWd (rho=0.306, p=0.002), IVSd (rho=0.395, p<0.001), moderate-severe MR (rho=0.276, p<0.005), LVMI (rho=0.300, p=0.002), relative wall thickness (RWT) (rho=0.271, p=0.006), QT duration (rho=0.213, p=0.034) and ST depression (rho=0.222, p=0.026). CONCLUSION: Specific biochemical, ECG, and ECHO characteristics can aid in the differentiation and early diagnosis of HCM and FD.

FUNDAMENTO: A cardiomiopatia hipertrófica (CMH) e a doença de Fabry (DF) são doenças herdadas geneticamente com características fenotípicas de hipertrofia ventricular esquerda (HVE) que causam resultados cardíacos adversos. OBJETIVOS: Investigar as diferenças demográficas, clínicas, bioquímicas, eletrocardiográficas (ECG) e ecocardiográficas (ECO) entre CMH e DF. MÉTODOS: 60 pacientes com CMH e 40 pacientes com DF foram analisados retrospectivamente como uma subanálise do "estudo LVH-TR" após exclusão de pacientes com fibrilação atrial, ritmo de estimulação, bloqueios de ramo e bloqueios atrioventriculares (AV) de segundo e terceiro graus. O nível de significância foi aceito como <0,05. RESULTADOS: O sexo masculino (p=0,048) e a creatinina (p=0,010) são significativamente maiores a favor da DF; entretanto, infradesnivelamento do segmento ST (p=0,028), duração do QT (p=0,041), espessura do septo interventricular (SIVd) (p=0,003), espessura da parede posterior (PWd) (p=0,009), insuficiência mitral moderada a grave (IM) (p=0,013) e o índice de massa ventricular esquerda (IMVE) (p=0,041) são significativamente maiores a favor da CMH nas análises univariadas. Na análise multivariada, a significância estatística apenas permanece na creatinina (p=0,018) e na duração do intervalo QT (0,045). A DF foi positivamente correlacionada com a creatinina (rho=0,287, p=0,004) e a CMH foi positivamente correlacionada com o PWd (rho=0,306, p=0,002), IVSd (rho=0,395, p<0,001), IM moderada-grave (rho= 0,276, p<0,005), IMVE (rho=0,300, p=0,002), espessura relativa da parede (ERP) (rho=0,271, p=0,006), duração do QT (rho=0,213, p=0,034) e depressão do segmento ST (rho =0,222, p=0,026). CONCLUSÃO: Características bioquímicas, ECG e ECO específicas podem auxiliar na diferenciação e no diagnóstico precoce da CMH e da DF.

The Definition of Sarcomeric and Non-Sarcomeric Gene Mutations in Hypertrophic Cardiomyopathy Patients: A Multicenter Diagnostic Study Across Türkiye.

BACKGROUND: Hypertrophic cardiomyopathy is a common genetic heart disease and up to 40%-60% of patients have mutations in cardiac sarcomere protein genes. This genetic diagnosis study aimed to detect pathogenic or likely pathogenic sarcomeric and non-sarcomeric gene mutations and to confirm a final molecular diagnosis in patients diagnosed with hypertrophic cardiomyopathy. METHODS: A total of 392 patients with hypertrophic cardiomyopathy were included in this nationwide multicenter study conducted at 23 centers across Türkiye. All samples were analyzed with a 17-gene hypertrophic cardiomyopathy panel using next-generation sequencing technology. The gene panel includes ACTC1, DES, FLNC, GLA, LAMP2, MYBPC3, MYH7, MYL2, MYL3, PLN, PRKAG2, PTPN11, TNNC1, TNNI3, TNNT2, TPM1, and TTR genes. RESULTS: The next-generation sequencing panel identified positive genetic variants (variants of unknown significance, likely pathogenic or pathogenic) in 12 genes for 121 of 392 samples, including sarcomeric gene mutations in 30.4% (119/392) of samples tested, galactosidase alpha variants in 0.5% (2/392) of samples and TTR variant in 0.025% (1/392). The likely pathogenic or pathogenic variants identified in 69 (57.0%) of 121 positive samples yielded a confirmed molecular diagnosis. The diagnostic yield was 17.1% (15.8% for hypertrophic cardiomyopathy variants) for hypertrophic cardiomyopathy and hypertrophic cardiomyopathy phenocopies and 0.5% for Fabry disease. CONCLUSIONS: Our study showed that the distribution of genetic mutations, the prevalence of Fabry disease, and TTR amyloidosis in the Turkish population diagnosed with hypertrophic cardiomyopathy were similar to the other populations, but the percentage of sarcomeric gene mutations was slightly lower.

Prevalence of Fabry Disease in patients with left ventricular hypertrophy in Turkey: Multicenter study (LVH-TR subgroup analysis).

PURPOSE: In this prospective study we aimed to determine the rate of Fabry Disease (FD) in patients with left ventricular hypertrophy (LVH), and to evaluate the clinical presentations of patients with FD in a comprehensive manner. In addition, we aimed to raise awareness about this issue by allowing early diagnosis and treatment of FD. METHODS: Our study was planned as national, multicenter, observational. Totally 22 different centers participated in this study. A total of 886 patients diagnosed with LVH by echocardiography (ECHO) were included in the study. Demographic data, biochemical parameters, electrocardiography (ECG) findings, ECHO findings, treatments and clinical findings of the patients were recorded. Dry blood samples were sent from male patients with suspected FD. The α-Gal A enzyme level was checked and genetic testing was performed in patients with low enzyme levels. Female patients suspected of FD were genetically tested with the GLA Gene Mutation Analysis. RESULTS: FD was suspected in a total of 143 (16.13%) patients included in the study. The α-Gal-A enzyme level was found to be low in 43 (4.85%) patients whom enzyme testing was requested. GLA gene mutation analysis was positive in 14 (1.58%) patients. Male gender, E/e' mean ,and severe hypertrophy are important risk factor for FD. CONCLUSION: In daily cardiology practice, FD should be kept in mind not only in adult patients with unexplained LVH but also in the entire LVH population. Dry blood test (DBS) should be considered in high-risk patients, and mutation analysis should be considered in required patients.

Evaluation of demographic, clinical, and aetiological data of patients admitted to cardiology clinics and diagnosed with left ventricular hypertrophy in Turkish population (LVH-TR).

BACKGROUND: Left ventricular hypertrophy (LVH) is potentially modifiable cardiovascular risk factor often overlooked in clinical practice. For this reason, we planned to LVH-TR (Left Ventricular Hypertrophy in Turkish Population) trial to determine the aetiological causes and demographic characteristics of LVH patients. METHODS: Our study was a multicentre, national, observational study and included 886 patients who applied to the cardiology clinics in 22 centres between February 2020 and August 2021. In the initial evaluation, the Fabry disease (FD) and cardiac amyloidosis (CA) algorithm was followed in patients whose definitive etiologic cause(s) could not be identified. RESULTS: The most common aetiological causes of LVH in our study were hypertension with a rate of 56.6%, heart valve disease with 8.2%, and hypertrophic cardiomyopathy with 7.5%. Athlete's heart was detected in eight patients, LV non-compaction was detected in four patients. The rate of LVH of unknown cause was 18.8%. FD was suspected in 143 patients, and CA was suspected in 16 patients. There were 43 (4.85%) patients with low α-galactosidase A enzyme levels. GLA gene mutation analysis was positive in 1.58% of all patients, and these patients were diagnosed with FD, and 15 (1.69%) patients were diagnosed with CA by endomyocardial biopsy method. CONCLUSION: In the aetiology of LVH, the rate of LVH of unknown cause was high. FD and CA should be considered primarily in this patient group. Early diagnosis of the disease by following the schemes leading to FD and CA was essential in starting treatment before the progression of the disease.

Mid-term survivals of cemented calcar-replacement bipolar hemiarthroplasty for unstable intertrochanteric fractures in elderly patients.

BACKGROUND: The literature has limited evidence regarding the mid-term survivals of cemented calcar-replacement bipolar hemiarthroplasty (HA) in elderly patients with unstable intertrochanteric (IT) fracture. The purpose of the present study was to evaluate clinical and radiological outcomes of cemented calcar-replacement bipolar HA for unstable IT fractures in elderly patients. METHODS: One hundred and twenty-two patients with the mean age of 80.6 years were enrolled in this retrospective study after they met the selection criteria. Demographics, main clinical characteristics, and operative data were recorded for all patients. Functional outcomes were assessed according to Koval's categories. Clinical and radiological evaluations were performed. Kaplan-Meier survival analysis was used to construct the cumulative survival rate. The mean follow-up time was 25.7 ±â€¯2.9 months (ranges 0-72 months). RESULTS: Based on Koval's categories, 3 or 4-level decrease was detected in 21 patients (17%). Three patients (2 periprosthetic infections, 1 periprosthetic fracture) underwent reoperation during follow-up. No patient underwent revision of bipolar HA prosthesis. Femoral stem loosening and stem subsidence was the most common complication, observed in 22 patients (18%), followed by acetabular erosion that was seen in 12 patients (9.8%). The mean cumulative survival rate of prosthesis was 56.5% (95% confidence interval: 51.3-61.6). CONCLUSION: Based on the results of our study, cemented calcar-replacement HA is an appropriate treatment option in elderly patients with unstable IT fractures owing to the advantages of satisfactory functional outcomes and lower reoperation rates. However, orthopedic surgeons should consider the low survival rates of cemented calcar-replacement HA prosthesis because of the increased femoral loosening in osteoporotic elderly patients.

Comparative evaluation of postoperative health status and functional outcome in patients treated with either proximal femoral nail or hemiarthroplasty for unstable intertrochanteric fracture.

PURPOSE: This study aimed to compare functional recovery and change in morbidity status from the preoperative levels among patients who underwent two different surgical treatments for unstable intertrochanteric fracture. METHODS: This retrospective comparative study enrolled 140 patients (aged >80 years) who were referred to two hospitals. Of these, 64 were treated using proximal femoral nail (PFN) and 76 were treated using hemiarthroplasty (HA). To evaluate functional recovery, primary outcome measures were cumulative illness rating scale (CIRS) score to evaluate changes in morbidity status, activity of daily living (ADL) index, and mobility scores. RESULTS: The proportion of patients who experienced increased CIRS scores in the HA group was higher at the 3-month follow-up (p = 0.02) but similar at the 6-month follow-up (p = 0.2) in comparison to the PFN group. Treatment with HA, American Society of Anesthesiologists scores of 3-4, and lower, preoperative ADL indexes were the major predictors of increased postoperative CIRS score. Impaired ambulatory ability and the need for walking aids were significantly higher in the PFN group at the 3-month follow-up (p = 0.01 and p = 0.02, respectively) but similar at the 6-month follow-up with respect to the HA group. PFN treatment and high patient body mass index were the major predictors of decreased ambulatory ability at postoperative 3 months. CONCLUSION: HA has several advantages, including early mobilization and decreased dependency. However, it is associated with greater blood loss, a higher need for blood transfusion, and longer surgical duration than PFN, all of which are predisposing factors for significantly higher risk of reduced CIRS scores.

What Are the Determinants of Mortality After Cemented Bipolar Hemiarthroplasty for Unstable Intertrochanteric Fractures in Elderly Patients?

BACKGROUND: Primary hemiarthroplasty is proposed for the treatment of unstable intertrochanteric fractures in elderly patients with the advantages of early mobilization, acceptable functional results, and lower failure rates. The 1-year mortality rates demonstrated high variance in the literature, whereas, the factors related to 1-year mortality were not widely investigated. The main purpose of the present study was to determine predictive factors related to 1-year mortality after primary cemented calcar-replacement bipolar hemiarthroplasty performed for unstable intertrochanteric fracture. METHODS: One hundred six patients with the mean age of 80.7 years were included in this retrospective study. Age, gender, body mass index, comorbid diseases, American Society of Anesthesiologists score, total hospitalization time, time from injury to surgery, operation time, estimated blood loss, postoperative mobilization time, and decrease in Koval ambulatory categories were evaluated. Univariate and multivariate analyses were performed to determine major predictors of 1-year mortality. The Kaplan-Meier survival analysis was used to construct the cumulative survival rate. RESULTS: Three or more American Society of Anesthesiologists scores, presence of ≥3 comorbid diseases, and postoperative mobilization time of ≥2 days were significantly correlated with 1-year mortality. Presence of ≥3 comorbid systemic diseases was identified as the major predictive factor for 1-year mortality. The overall 5-year cumulative survival rate was 5.6%. CONCLUSION: Having three or more comorbid systemic diseases has been detected as the major determinant of 1-year mortality after primary cemented calcar-replacement bipolar hemiarthroplasty performed for unstable intertrochanteric fracture in elderly patients.