Prognostic value of pulmonary artery diameter/aorta diameter ratio in patients with acute pulmonary embolism.

BACKGROUND: The ratio of pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) has been reported to be a prognostic marker in several lung diseases; however, the usefulness of this tool in patients with acute pulmonary embolism (APE) is unknown. Here, we aimed to determine the long-term prognostic value of the PAD/AoD ratio in patients with APE. METHODS: A total of 275 patients diagnosed with APE at our tertiary care center between November 2016 and February 2022 were included in the study. The patients were divided into two groups according to the presence of long-term mortality and their PAD/AoD ratios were compared. RESULTS: Long-term mortality was observed in 48 patients during the median follow-up of 59 (39-73) months. The patients were divided into two groups for analysis: group 1, consisting of 227 patients without recorded mortality, and group 2, consisting of 48 patients with documented mortality. A multivariate Cox regression model indicated that the PAD/AoD ratio has the potential to predict long-term mortality (HR: 2.9116, 95% CI: 1.1544-7.3436, p = 0.023). Analysis of the receiver operating characteristic curve revealed that there was no discernible difference in discriminative ability between the simplified pulmonary embolism severity index (sPESI) and PAD/AoD ratio (area under the curve [AUC] = 0.679 vs. 0.684, respectively, p = 0.937). The long-term predictive ability of the PAD/AoD ratio was not inferior to the sPESI score. CONCLUSIONS: The PAD/AoD ratio, which can be easily calculated from pulmonary computed tomography, may be a useful parameter for determining the prognosis of APE patients.

Examining the relationship between genetic polymorphisms (BDKRB2, GNB3, HIF1A, MCT1, NOS3) and endurance athlete status.

PURPOSE: Genetic factors are important in terms of athletic performance. Recent studies to determine the relationship between the genes that lead to physiological responses have attracted attention. In this respect, this meta-analysis study was designed to examine the relationship between genetic polymorphism (BDKRB2 rs5810761, GNB3 rs5443, HIF1A rs11549565, MCT1 rs1049434, NOS3 rs2070744) and endurance athlete's status. METHODS: The search included studies published from 2009 to 2022. To determine the relevant studies, Pubmed, Web of Science databases were systematically scanned. Only case-control studies were included in the meta-analysis. To determine the relevant studies, Pubmed, Web of Science databases were systematically scanned, and a total of 31 studies met the criteria for inclusion in the meta-analysis. Relevant data from the included studies were collected and analyzed using a random effects or fixed effects model. The effect size was calculated as the odds ratio or a risk ratio the corresponding 95% confidence intervals. RESULTS: According to the results of the analysis, BDKRB2 rs5810761 + 9 allele, and NOS3 rs2070744 T allele were significantly more prevalent in endurance athletes (p < 0.05). Genotype distributions of BDKRB2 rs5810761, MCT1 rs1049434, and NOS3 rs2070744 showed significant differences in the dominant model (p < 0.05). However, no significant association was found between endurance athlete status and GNB3 rs5443 and HIF1A rs11549465 polymorphisms. CONCLUSION: These results show that some gene polymorphisms play an important role in endurance athlete status and suggest that having a specific genetic basis may also confer a physiological advantage for performance.

The Association between Exercise-Induced Ventricular Premature Contractions and Long-Term Mortality in Patients without Obstructive Coronary Artery Disease.

Background: The treadmill exercise test is widely used to determine cardiovascular risk and mortality. Premature ventricular complexes (PVCs) are frequently observed during exercise stress testing. The literature on the role of PVCs observed during treadmill exercise testing in predicting prognosis is controversial. Hence, we aimed to evaluate the clinical results of PVCs seen during exercise testing in patients without obstructive coronary artery disease confirmed by coronary angiography (CAG). Methods: The study population consisted of 1624 consecutive patients who were considered high risk according to the Duke treadmill risk score and had no significant stenosis on CAG from January 2016 to April 2021. The primary endpoints of the study were long-term all-cause mortality of patients who had PVCs during the exercise test or during the resting phase. Results: Long-term mortality was observed in 53 of the 1624 patients after a mean follow-up of 47 months. PVCs were observed in 293 (18.7%) patients without long-term mortality, and in 24 (45.3%) patients with long-term mortality (p < 0.001). The model adjusted for all covariates showed that the presence of PVCs in the recovery phase [p < 0.007, hazard ratio (HR) (95% confidence interval (CI)) 2.244 (1.244-4.047)] and advanced age [p < 0.001, HR (95% CI) 1.194 (1.143-1.247)] were associated with long-term all-cause mortality. Conclusions: PVCs observed during treadmill exercise testing and the recovery phase were related to long-term mortality in patients without obstructive coronary artery disease.

Evaluation of Naples prognostic score to predict long-term mortality in patients with pulmonary embolism.

Background: The Naples prognostic score (NPS), which reflects the inflammatory and nutritional status of patients, is often used to determine prognosis in cancer patients. The aim of this study was to determine the long-term prognostic value of the NPS in acute pulmonary embolism (APE) patients. Methods: Two hundred thirty-nine patients diagnosed with APE were divided into two groups according to their NPS, and long-term mortality was compared. Results: The long-term mortality was observed in 38 patients out of 293 patients in the mean follow-up of 24 months. Multivariate analysis showed that NPS as a categorical parameter and NPS as a numeric parameter were independent predictors of long-term mortality. Conclusion: This study highlights that NPS may have the potential to predict long-term mortality in APE patients.

Endoscopic Thoracic Sympathectomy in the Treatment of Vasospastic Angina Resistant to Medical Therapy.

BACKGROUND: In this study, we aimed to investigate the clinical follow-up results of endoscopic thoracic sympathectomy (ETS) in the treatment of vasospastic angina (VSA) resistant to maximal medical therapy. METHODS: A total of 80 patients with VSA who presented to our hospital between 2010 and 2022 were included in our study. Among them, 6 patients who did not respond to medical therapy underwent ETS. In-hospital and long-term clinical outcomes of patients who underwent ETS were recorded. RESULTS: The median age of the patients with VSA was 57 [48-66] years, and 70% of the group were males. In the ETS group, compared to the non-ETS group, higher numbers of hospital admissions and coronary angiographies were observed before ETS (median 6 [5-6] versus 2 [1-3], P <.001; median 5 [3-6] versus 2 [1-3], P =.004, respectively). Additionally, while 2 patients (33.3%) in the ETS group had implantable cardioverter defib-rillator (ICD), only 2 patients (2.7%) in the non-ETS group had ICD (P =.027). Out of the 6 patients who underwent ETS, 2 were females, with a median age of 56 [45-63] years. Four patients underwent successful bilateral ETS, while 2 patients underwent unilateral ETS. During the follow-up period after ETS, only 3 patients experienced sporadic attacks (once in 28 months, twice in 41 months, and once in 9 years, respectively), while no attacks were observed in 3 patients during their median follow-up of 7 years. CONCLUSION: It appears that ETS is effective in preventing VSA attacks without any major complications.

The Role of AGT, AMPD1, HIF1α, IL-6 Gene Polymorphisms in the Athletes' Power Status: A Meta-Analysis.

This meta-analysis was designed to investigate the relationship between genetic polymorphisms (AGT rs699, AMPD1 rs17602729, HIF1α rs11549465, IL-6 rs1800795) and power athletes' status. Only case-control studies were included in the meta-analysis. A systematic search of the PubMed and Web of Science databases was performed to identify relevant studies and 23 studies met the inclusion criteria for the meta-analysis. The data from the included studies were pooled and analyzed using a random effects or fix effects model. The effect size was calculated as the odds ratio or a risk ratio with 95% confidence intervals. The results showed that certain genetic polymorphisms, AGT rs699 Thr allele, HIF1A rs11549465 Ser allele and AMPD1 rs17602729 C allele, were significantly more prevalent in power athletes (p < 0.05). When examining the genotype frequency distribution of AGT rs699 and AMPD1 rs17602729, significant differences were found in both the dominant and recessive models (p < 0.05). The results indicate that these gene polymorphisms play a role in power athlete status, however, new and more comprehensive studies are needed to confirm these results.

Effect of ivabradine on ventricular arrhythmias in heart failure patients with reduced ejection fraction.

BACKGROUND/INTRODUCTION: Heart failure patients with reduced ejection fraction are at high risk for ventricular arrhythmias and sudden cardiac death. Ivabradine, a specific inhibitor of the If current in the sinoatrial node, provides heart rate reduction in sinus rhythm and angina control in chronic coronary syndromes. OBJECTIVE: The effect of ivabradine on ventricular arrhythmias in heart failure patients with reduced ejection fraction patients has not been fully elucidated. The aim of this study was to investigate the effect of ivabradine use on life-threatening arrhythmias and long-term mortality in heart failure patients with reduced ejection fraction patients. METHODS: In this retrospective study, 1,639 patients with heart failure patients with reduced ejection fraction were included. Patients were divided into two groups: ivabradine users and nonusers. Patients presenting with ventricular tachycardia, the presence of ventricular extrasystole, and ventricular tachycardia in 24-h rhythm monitoring, appropriate implantable cardioverter-defibrillator shocks, and long-term mortality outcomes were evaluated according to ivabradine use. RESULTS: After adjustment for all possible variables, admission with ventricular tachycardia was three times higher in ivabradine nonusers (95% confidence interval 1.5-10.2). The presence of premature ventricular contractions and ventricular tachycardias in 24-h rhythm Holter monitoring was notably higher in ivabradine nonusers. According to the adjusted model for all variables, 4.1 times more appropriate implantable cardioverter-defibrillator shocks were observed in the ivabradine nonusers than the users (95%CI 1.8-9.6). Long-term mortality did not differ between these groups after adjustment for all covariates. CONCLUSION: The use of ivabradine reduced the appropriate implantable cardioverter-defibrillator discharge in heart failure patients with reduced ejection fraction patients. Ivabradine has potential in the treatment of ventricular arrhythmias in heart failure patients with reduced ejection fraction patients.

Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy and future perspectives.

BACKGROUND: The hypertrophic cardiomyopathy (HCM) risk- sudden cardiac death (SCD) model provides a convenient tool for determining the risk of SCD in patients with HCM even though some patients with low-risk scores still remain at risk of SCD. Hence, the aim of our study was to assess the performance of HCM Risk-SCD in a large series of consecutive patients with HCM who had been followed up in a tertiary center. METHODS: The study population consisted of 389 consecutive HCM patients who had been followed up between 2004 and 2021. Demographic and clinical characteristics, estimated 5-year risk using the HCM Risk-SCD model, were compiled, and survival data were collected during follow-up. Patients were divided into 2 groups according to their long-term survival, and HCM risk-SCD scores of these two groups were compared. RESULTS: The long-term mortality was observed in 47 patients out of 389 patients in the during a mean follow-up of 55.5 ± 12.7 months. The mean HCM Risk-SCD score of surviving patients was significantly lower than that of non-survivors (1.8% vs. 3.0%, p < .001). The HCM Risk-SCD score was above 6% in nine (2.6%) survivors and nine (19.1%) non-survivors (p < .001). The ROC curve based on the HCM Risk-SCD score had 61% sensitivity and 61% specificity for risk threshold of for 2.0%, 38% sensitivity and 99% specificity a threshold of ≥4%, 17% sensitivity, and 99% specificity for a threshold of ≥6%. CONCLUSION: A new risk algorithm with higher sensitivity is needed, although the HCM risk-SCD model is still quite useful in identifying patients at a high risk for SCD.

Efficiency of MVP ECG Risk Score for Prediction of Long-Term Atrial Fibrillation in Patients With ICD for Heart Failure With Reduced Ejection Fraction.

BACKGROUND AND OBJECTIVES: The morphology-voltage-P-wave duration (MVP) electrocardiography (ECG) risk score is a newly defined scoring system that has recently been used for atrial fibrillation (AF) prediction. The aim of this study was to evaluate the ability of the MVP ECG risk score to predict AF in patients with an implantable cardioverter defibrillator (ICD) and heart failure with reduced ejection fraction in long-term follow-up. METHODS: The study used a single-center, and retrospective design. The study included 328 patients who underwent ICD implantation in our hospital between January 2010 and April 2021, diagnosed with heart failure. The patients were divided into low, intermediate and high-risk categories according to the MVP ECG risk scores. The long-term development of atrial fibrillation was compared among these 3 groups. RESULTS: The low-risk group included 191 patients, the intermediate-risk group 114 patients, and the high-risk group 23 patients. The long-term AF development rate was 12.0% in the low-risk group, 21.9% in the intermediate risk group, and 78.3% in the high-risk group. Patients in the high-risk group were found to have 5.2 times higher rates of long-term AF occurrence compared to low-risk group. CONCLUSIONS: The MVP ECG risk score, which is an inexpensive, simple and easily accessible tool, was found to be a significant predictor of the development of AF in the long-term follow-up of patients with an ICD with heart failure with reduced ejection fraction. This risk score may be used to identify patients who require close follow-up for development and management of AF.

Primary Right Atrial Cardiac Angiosarcoma in Patient With Poland Syndrome: Case Report and Review of the Literature.

This article presents the case of a 24-year-old woman with Poland syndrome who developed primary right atrial cardiac angiosarcoma. The patient presented to the hospital with dyspnea and chest pain, and imaging studies revealed a large mass attached to the right atrium. Urgent surgery was performed to remove the tumor, and the patient underwent adjuvant chemotherapy afterward. Follow-up exams showed no signs of the tumor or any complications from treatment. Poland syndrome is a rare congenital disorder characterized by the absence of unilateral large pectoral muscle, ipsilateral symbrachydactyly, and other malformations of the anterior chest wall and breast. Although the condition does not predispose patients to malignancy, different pathologies can be seen in these patients due to the unknown etiology of the syndrome. Primary right atrial cardiac angiosarcoma is a rare malignancy, and its coexistence with Poland syndrome has not been well established in the literature. This case report highlights the need to consider cardiac angiosarcoma as a possible diagnosis in patients with Poland syndrome who present with cardiac symptoms.

Machine Learning Approach on High Risk Treadmill Exercise Test to Predict Obstructive Coronary Artery Disease by using P, QRS, and T waves' Features.

Treadmill Exercise Test (TET) results and patients' clinical symptoms influence cardiologists' decision to perform Coronary Angiography (CAG) which is an invasive procedure. Since TET has high false positive rates, it can cause an unnecessary invasive CAG. Our primary objective was to develop a machine learning model capable of optimizing TET performance based on electrocardiography (ECG) waves characteristics and signals. TET reports from 294 patients who underwent CAG following high risk TET were collected and categorized into those with critical CAD and others. The signal was converted to time series format. A dataset containing the P, QRS, and T wave times and amplitudes was created. Using this dataset, 5 machine learning algorithms were trained with 5-fold cross validation. All these models were then compared to the performance of cardiologists on V5 signal. The results from 5 machine learning models were clearly superior to the cardiologists' V5 signal performance (P < 0.0001). In addition, the XGBoost model, with an accuracy of 80.92±6.42% and an area under the curve (AUC) of 0.78±0.06, was the most successful model. Machine learning models can produce high-performance diagnoses using the V5 signal markers only as it does not require any clinical markers obtained from TET reports. This can lead to significant contributions to improving clinical prediction in non-invasive methods.

Comparison of ICSI and conventional IVF in non-male factor patients with less than four oocytes.

BACKGROUND: We aimed to analyse our clinical results for a particular subgroup of patients with poor ovarian response (POR) to clarify if lower number of oocytes is a drawback for proceeding to C-IVF. MATERIALS AND METHODS: In this retrospective study, patient files of all couples (#1733) who underwent oocyte retrieval between January 2017 and December 2019 were reviewed and 191 cases diagnosed with non-male factor infertility in which ≤ 3 cumulus-oocyte complexes available for fertilisation were analysed. Exclusion criteria were: woman age > 42, patients with a history of previous ART trial, prenatal genetic testing cycles and couples undergoing total cryopreservation for any indication. Three groups were constructed depending on the method of fertilisation and on semen quality as follows: IVF non-male factor (Group 1, n = 77); ICSI non-male factor (Group 2, n = 65); ICSI male factor-ICSI/MF n = 49 according to WHO reference values. Main outcome parameters were: fertilisation rate, implantation rate and live birth rate. RESULTS: Fertilisation rate per collected COC was significantly higher in group 1 compared to the other two groups (85.68%, 72.58%, 73.33% respectively, p = 0.004). FR per inseminated oocyte also tended to be higher in group 1 but not reaching a statistically significant level. Both techniques yielded similar implantation rates (20.42%, 28.49%, 23.33% respectively, p = 0.407) and live birth rates (26.8%, 30.6%, 31.1%, respectively, p = 0.643). CONCLUSION: In the presence of normal semen parameters, low egg number is not an indication to perform ICSI. The choice of fertilisation method should be based primarily on semen quality, in combination with the patient's previous history regardless of the ovarian reserve.

Predictors for early mortality in patients with implantable cardiac defibrillator for heart failure with reduced ejection fraction.

Implantable cardioverter defibrillators (ICD) are recommended in heart failure with reduced ejection fraction (HFrEF) patients to reduce arrhythmic deaths. This study aimed to identify risk factors associated with mortality within one-year following the ICD. The data from our hospital's electronic database system was extracted for patients who were implanted ICD secondary to HFrEF between 2009 and 2019. Overall, 1107 patients were included in the present analysis. Mortality rate at one-year following the device implantation was 4.7%. In multivariate analysis; age, atrial fibrillation, New York Heart Association classification >2, blood urea nitrogen, pro-brain natriuretic peptide and albumin independently predicted one year mortality.

Evaluating systemic immune-inflammation index in patients with implantable cardioverter defibrillator for heart failure with reduced ejection fraction.

BACKGROUND: Pro-inflammatory pathways play an important role in the follow-ups of patients with intracardiac defibrillators (ICDs) for heart failure (HF) reduced with ejection fraction (HFrEF). A newly defined index - the systemic immune-inflammation index (SII)-has recently been reported to have prognostic value in patients with cardiovascular disease. This study's aim is to evaluate the SII value regarding its association with long-term mortality and appropriate ICD therapy during a 10-year follow-up. METHODS: This retrospective study included 1011 patients with ICD for HFrEF. The SII was calculated as the neutrophil-to-lymphocyte ratio × total platelet count in the peripheral blood. The study population was divided into two groups according to the SII's optimal cut-off value to predict long-term mortality. The long-term prognostic impact of SII on these patients was evaluated regarding mortality and appropriate ICD therapy. RESULTS: The patients with a higher SII (≥1119) had significantly higher long-term mortality and appropriate ICD therapy rates. After adjustment for all confounding factors, the long-term mortality rate was 5.1 for a higher SII. (95% CI: 2.9-8.1). The long-term appropriate ICD therapy rate was 2.0 for a higher SII (95% CI: 1.4-3.0). CONCLUSION: SII may be an independent predictive marker for both long-term mortality and appropriate ICD therapy in patients with HFrEF.

Comparison of mortality prediction scores in elderly patients with ICD for heart failure with reduced ejection fraction.

BACKGROUND: This investigation aimed to examine and compare the predictive value of MADIT-II, FADES, PACE and SHOCKED scores in predicting one-year and long-term all-cause mortality in implantable cardioverter-defibrillator (ICD) implanted patients, 75 years old and older, since there has been an area of uncertainty about the utility and usefulness of these available risk scores in such cases. METHODS: In this observational, retrospective study, 189 ICD implanted geriatric patients were divided into two groups according to the presence of long-term mortality in follow-up. The baseline characteristics and laboratory variables were compared between the groups. MADIT-II, FADES, PACE and SHOCKED scores were calculated at the time of ICD implantation. One-year and long-term predictive values of these scores were compared by a receiver-operating curve (ROC) analysis. RESULTS: A ROC analysis showed that the best cutoff value of the MADIT-II score to predict one-year mortality was ≥ 3 with 87% sensitivity and 74% specificity (AUC 0.83; 95% CI 0.73-0.94; p < 0.001) and that for long-term mortality was ≥ 2 with 83% sensitivity and 43% specificity (AUC 0.68; 95% CI 0.60-0.76; p < 0.001). The predictive value of MADIT-II was superior to FADES, PACE and SHOCKED scores in ICD implanted patients who are 75 years and older. CONCLUSION: MADIT-II score has a significant prognostic value as compared to FADES, PACE and SHOCKED scores for the prediction of one-year and long-term follow-up in geriatric patients with implanted ICDs for heart failure with reduced ejection fraction.

Clinical and Hormonal Profiles Correlate With Molecular Characteristics in Patients With 11ß-Hydroxylase Deficiency.

BACKGROUND: Given the rarity of 11ß-hydroxylase deficiency (11ßOHD), there is a paucity of data about the differences in clinical and biochemical characteristics of classic (C-11ßOHD) and nonclassic 11ßOHD (NC-11ßOHD). OBJECTIVE: To characterize a multicenter pediatric cohort with 11ßOHD. METHOD: The clinical and biochemical characteristics were retrospectively retrieved. CYP11B1 gene sequencing was performed. Seventeen plasma steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. RESULTS: 102 patients (C-11ßOHD, n = 92; NC-11ßOHD, n = 10) from 76 families (46,XX; n = 53) had biallelic CYP11B1 mutations (novel 9 out of 30). Five 46,XX patients (10%) were raised as males. Nineteen patients (19%) had initially been misdiagnosed with 21-hydroxylase deficiency. Female adult height was 152 cm [-1.85 SD score (SDS)] and male 160.4 cm (-2.56 SDS).None of the NC-11ßOHD girls had ambiguous genitalia (C-11ßOHD 100%), and none of the NC-11ßOHD patients were hypertensive (C-11ßOHD 50%). Compared to NC-11ßOHD, C-11ßOHD patients were diagnosed earlier (1.33 vs 6.9 years; P < 0.0001), had higher bone age-to-chronological age (P = 0.04) and lower adult height (-2.46 vs -1.32 SDS; P = 0.05). The concentrations of 11-oxygenated androgens and 21-deoxycortisol were low in all patients. The baseline ACTH and stimulated cortisol were normal in NC-11ßOHD. Baseline cortisol; cortisone; 11-deoxycortisol; 11-deoxycorticosterone and corticosterone concentrations; and 11-deoxycortisol/cortisol, 11-deoxycorticosterone/cortisol, and androstenedione/cortisol ratios were higher in C-11ßOHD than NC-11ßOHD patients (P < 0.05). The 11-deoxycortisol/cortisol ratio >2.2, <1.5, and <0.1 had 100% specificity to segregate C-11ßOHD, NC-11ßOHD, and control groups. CONCLUSION: NC-11ßOHD can escape from clinical attention due to relatively mild clinical presentation. However, steroid profiles enable the diagnosis, differential diagnosis, and subtyping of 11ßOHD.

The value of C-reactive protein-to-albumin ratio in predicting long-term mortality among HFrEF patients with implantable cardiac defibrillators.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) who received implantable cardiac defibrillator (ICD) still remain at high risk due to pump failure and prevalent comorbid conditions. The primary aim of this research was to evaluate the predictive value of C-reactive protein-to-albumin ratio (CAR) for all-cause mortality among patients with HFrEF despite ICD implantation. MATERIALS AND METHODS: Those who were implanted ICD for HFrEF in our institution between 2009 and 2019 were included. Data were extracted from hospital's database. CAR was calculated as ratio of C-reactive protein (CRP) to serum albumin concentration. Patients were grouped into tertiles in accordance with CAR at the time of the implantation. During follow-up duration of 38 [17-77] months, survival times of tertiles were compared by using Kaplan-Meier survival method. Forward Cox proportional regression model was used for multivariable analysis. RESULTS: Thousand and eleven patients constituted the study population. Ischaemic cardiomyopathy was the primary diagnosis in 92.3%, and ICD was implanted for the primary prevention among 33.9% of patients. Of those, 14.5% died after the discharge. Patients in tertile 3 (T3) had higher risk of mortality (4.2% vs 11.0% vs 28.5%) compared with those in other tertiles. Multivariable analysis revealed that when patients in T1 were considered as the reference, both those in T2 and those in T3 had independently higher risk of all-cause mortality. This finding was consistent in the unadjusted and adjusted multivariable models. CONCLUSION: Among patients with HFrEF and ICD, elevated CAR increased the risk of all-cause mortality at long term.

Prognostic nutritional index as the predictor of long-term mortality among HFrEF patients with ICD.

BACKGROUND: The benefit of implantable cardiac defibrillator (ICD) in patients with heart failure and reduced ejection fraction (HFrEF) could be limited in a particular group of patients. Low prognostic nutritional index (PNI) indicates malnutrition and proinflammatory condition. We sought to investigate the value of PNI in predicting long-term mortality among HFrEF patients with ICD. METHODS: Electronic database was searched for identifying patients with HFrEF who were implanted ICD in our institution between 2009 and 2019. Demographic and clinical characteristics of included patients were recorded. PNI was calculated according to the formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3 ). Patients were divided into the quartiles according to PNI values. Differences between the groups were analyzed by the log-rank test. A forward Cox proportional regression model was used for multivariable analysis. RESULTS: One thousand and hundred patients were included to the study. The underlying heart failure etiology was ischemic and nonischemic in 77.3% and 22.7% of patients, respectively. Mortality rate in Q1 (5.1%) was considered as the reference. In the unadjusted model the mortality rate was 9.5% (hazard ratio [HR] 1.76, 95% confidence interval [95% CI] [0.92-3.38]) in Q2, 10.2% (HR 1.88, 95% CI 0.99-3.58) in Q3, and 39.6% (HR 8.12, 95% CI 4.65-14.17) in Q4. The same trend was consistent in the age- and sex-adjusted, comorbidities-adjusted, and covariates-adjusted models. CONCLUSION: Among patients who were implanted with ICD secondary to HFrEF, lower PNI value predicted all-cause mortality during long-term follow-up. This is the first study demonstrating the value of PNI in this population.

Co-existence of Congenital Adrenal Hyperplasia and Familial Hypokalemic Periodic Paralysis due to CYP21A2 and SCN4A Pathogenic Variants

Steroid 21-hydroxylase deficiency is the most common cause of congenital adrenal hyperplasia (CAH), usually due to biallelic variants in CYP21A2. Classical 21-hydroxylase deficiency is characterised by virilisation of the external genitalia in females and hypocortisolism. Hyponatremia and hyperkalemia are among the common biochemical findings. Familial hypokalemic periodic paralysis (FHPP) is a rare disorder in which affected individuals may experience paralytic episodes associated with hypokalemia, caused by pathogenic variants in SCN4A or CACNA1S. A 14-year-old female, who had been diagnosed with classical 21-hydroxylase deficiency and treated with hydrocortisone and fludrocortisone since early infancy, presented with acute onset weakness. The laboratory results revealed a remarkably low serum potassium level. The family history revealed that both her father and uncle had the same hypokalemic symptoms, which suggested an FHPP diagnosis. We found two previously reported homozygous variants in the CYP21A2 (p.Ile173Asn) and SCN4A (p.Arg672His) genes in the patient. Therefore, diagnoses of simple virilising 21-hydroxylase deficiency and FHPP were genetically confirmed. Here, FPHH and chronic overtreatment with fludrocortisone may explain the presentation of our patient with severe hypokalemia. The family's medical history, which is always a valuable clue, should be investigated in detail since rare inherited conditions may co-occur in geographies where consanguineous marriages are common and the genetic pool is diverse. In patients with CAH, care should be taken to avoid overtreatment with fludrocortisone. Androgens may have triggered the hypokalemic attack in FHPP, as supported in a previous study.

The Effectiveness of Sirolimus Treatment in Two Rare Disorders with Nonketotic Hypoinsulinemic Hypoglycemia: The Role of mTOR Pathway

Nonketotic-hypoinsulinemic hypoglycemia (NkHH) is a very rare problem charcterized by increase in glucose consumption without hyperinsulinism. This disorder has mainly been reported in cases with AKT2 mutation and rarely in cases with PTEN mutation. In cases with PTEN or AKT2 mutation, there is no effective therapy other than frequent feeding to counter hypoglycemia. The mammalian target of rapamicin (mTOR) inhibitor, sirolimus, has been used in hyperinsulinemic hypoglycemia that was unresponsive to other medical treatment. In the insulin signaling pathway, both AKT2 and PTEN function upstream of mTOR. However, the role of Sirolimus on hypoglycemia in AKT2 and PTEN mutations is unknown. Case 1: Six month-old female with AKT2 mutation [c.49G>A (p.E17K)] and evidence of NkHH. Frequent feeding was unsuccesful in correcting hypoglycemia and her proptosis continued to worsen. Sirolimus treatment was started at three years of age. Subsequently, blood glucose (BG) levels increased to normal levels. Case 2: In a male with PTEN mutation (p.G132V (c.395G>T), persistent NkHH started at 16 years of age (fasting BG: 27 mg/dL, fasting insulin 1.5 mmol/L, while ketone negative). Sirolimus treatment was started and hypoglycemia was succesfully controlled. NkHH is a very rare and serious disorder which is challenging, both for diagnosis and treatment. Additionally, AKT2 and PTEN mutations may result in NkHH. Sirolimus treatment, through mTOR inhibition, appeared to be effectively controlling the peristent hypoglycemia and may be a life-saving therapy in this NkHH due to AKT2 and PTEN mutations.