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.

Long-Term Prognosis of Patients with Heart Failure: Follow-Up Results of Journey HF-TR Study Population.

BACKGROUND: Despite advances in therapeutic management of patients with heart failure, there is still an increasing morbidity and mortality all over the world. In this study, we aimed to present the 3-year follow-up outcomes of patients included in the Journey HF-TR study in 2016 that has evaluated the clinical characteristics and management of patients with acute heart failure admitted to the hospital and present a national registry data. METHODS: The study was designed retrospectively between November 2016 and December 2019. Patient data included in the previously published Journey HF-TR study were used. Among 1606 patients, 1484 patients were included due to dropout of 122 patients due to inhospital death and due to exclusion of 173 due to incomplete data. The study included 1311 patients. Age, gender, concomitant chronic conditions, precipitating factors, New York Heart Association, and left ventricular ejection fraction factors were adjusted in the Cox regression analysis. RESULTS: During the 3-year follow-up period, the ratio of hospitalization and mortality was 70.5% and 52.1%, respectively. Common causes of mortality were acute decompensation of heart failure and acute coronary syndrome. Angiotensin receptor blockers, betablockers, statin, and sacubitril/valsartan were found to reduce mortality. Hospitalization due to acute decompensated heart failure, acute coronary syndrome, lung diseases, oncological diseases, and cerebrovascular diseases was associated with the increased risk of mortality. Implantation of cardiac devices also reduced the mortality. CONCLUSIONS: Despite advances in therapeutic management of patients with heart failure, our study demonstrated that the long-term mortality still is high. Much more efforts are needed to improve the inhospital and long-term survival of patients with chronic heart failure.

Evaluation of Aortic Elasticity Parameters in Survivors of COVID-19 Using Echocardiography Imaging.

OBJECTIVE: While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects lung tissue, it may cause direct or indirect damage to the cardiovascular system, and permanent damage may occur. Arterial stiffness is an early indicator of cardiovascular disease risk. The aim of our study was to establish the potential effects of SARS-CoV-2 on the vascular system evaluated by transthoracic echocardiographic examination. SUBJECTS AND METHODS: This study compared arterial stiffness between the survivors of COVID-19 and those without a history of COVID-19 infection. The difference in aortic diameter was examined using echocardiography. RESULTS: The study included 50 patients who survived COVID-19 in the last 3-6 months and 50 age- and gender-matched healthy volunteers. In surviving COVID-19 patients, aortic diastolic diameter in cm ([3.1 ± 0.2] vs. [2.9 ± 0.1], p < 0.001), pulse pressure (PP) ([43.02 ± 14.05] vs. [35.74 ± 9.86], p = 0.004), aortic distensibility ([5.61 ± 3.57] vs. [8.31 ± 3.82], p < 0.001), aortic strain ([10.56 ± 4.91] vs. [13.88 ± 5.86], p = 0.003), PP/stroke volume index ([1.25 ± 0.47] vs. [0.98 ± 0.28], p = 0.001), and aortic stiffness index ([2.82 ± 0.47] vs. [2.46 ± 0.45], p < 0.001) were statistically significant compared to the control group. CONCLUSION: SARS-CoV-2 may cause reduced or impaired aortic elasticity parameters linked to impaired arterial wall function in COVID-19 survivors compared with controls.

Time delays in each step from symptom onset to treatment in acute myocardial infarction: Results from a nation-wide TURKMI registry.

OBJECTIVE: In this study, we aimed to analyze the TURKMI registry to identify the factors associated with delays from symptom onset to treatment that would be the focus of improvement efforts in patients with acute myocardial infarction (AMI) in Turkey. METHODS: The TURKMI study is a nation-wide registry that was conducted in 50 centers capable of 24/7 primary percutaneous coronary intervention (PCI). All consecutive patients (n=1930) with AMI admitted to coronary care units within 48 hours of symptom onset were prospectively enrolled during a predefined 2-week period between November 1, 2018, and November 16, 2018. All the patients were examined in detail with regard to the time elapsed at each step from symptom onset to initiation of treatment, including door-to-balloon time (D2B) and total ischemic time (TIT). RESULTS: After excluding patients who suffered an AMI within the hospital (2.6%), the analysis was conducted for 1879 patients. Most of the patients (49.5%) arrived by self-transport, 11.8% by emergency medical service (EMS) ambulance, and 38.6% were transferred from another EMS without PCI capability. The median time delay from symptom-onset to EMS call was 52.5 (15-180) min and from EMS call to EMS arrival 15 (10-20) min. In ST-segment elevation myocardial infarction (STEMI), the median D2B time was 36.5 (25-63) min, and median TIT was 195 (115-330) min. TIT was significantly prolonged from 151 (90-285) min to 250 (165-372) min in patients transferred from non-PCI centers. The major significant factors associated with time delay were patient-related delay and the mode of hospital arrival, both in STEMI and non-STEMI. CONCLUSION: The baseline evaluation of the TURKMI study revealed that an important proportion of patients presenting with AMI within 48 hours of symptom onset reach the PCI treatment center later than the time proposed in the guidelines, and the use of EMS for admission to hospital is extremely low in Turkey. Patient-related factors and the mode of hospital admission were the major factors associated with the time delay to treatment.

Relation Between Globulin, Fibrinogen, and Albumin With the Presence and Severity of Coronary Artery Disease.

The albumin to globulin ratio (AGR) is used as a prognostic marker in acute ischemic cardiovascular events. We investigated whether serum AGR, fibrinogen, and fibrinogen to albumin ratio (FAR) are related to the presence and severity of coronary artery disease (CAD). Patients who underwent coronary angiography procedures were analyzed retrospectively. The severity of CAD was assessed by the Gensini score. The study population (3031 patients; 1071 females and 1960 males) was divided into 3 tertiles based on AGR values. Gensini score, lipid levels, diabetes mellitus (DM), hypertension (HT), age, and fibrinogen level were higher in the low AGR group. Pearson correlation analysis showed that AGR (r = -0.068, P < .001) was negatively and fibrinogen (r = 0.187, P < .001) was positively correlated with the Gensini score. Male gender, HT, smoking, DM, age, high triglyceride (TG) level, low-density lipoprotein cholesterol (LDL-C) >160 mg/dL, estimated glomerular filtration rate (eGFR) <60 mL/min, and fibrinogen level >3.5 g/L were independent predictors of CAD. Male gender, age, eGFR, DM, LDL-C, TG, and FAR had an independent positive relation to the Gensini score. In conclusion, similar to traditional risk factors, plasma fibrinogen and albumin levels showed a close relation with the presence and severity of CAD.

Unilateral peripheral slow flow phenomenon without significant stenosis in lower extremity artery: can primary peripheral slow flow be a new phenomenon?

Peripheral artery disease affects nearly a quarter billion of the world's population, and it is one of the most important causes of decreased quality of life. Primary peripheral slow flow without significant stenosis in peripheral arteries has not been previously reported in the literature. In this case report, we present a slow flow phenomenon that extended from the right external iliac artery to the distal peripheral bed observed during peripheral angiography in a patient who exhibited pain and claudication in the right lower extremity after walking 50 m. Medical treatment provided symptomatic improvement in coronary slow flow and led to a decrease in claudication. Future randomised controlled studies conducted on patients with suspected peripheral slow flow phenomenon would increase our knowledge on both the aetiology and treatment of this condition.

Association of abnormal coronary sinus reflux with coronary slow flow and importance of the Thebesian valve.

BACKGROUND: The relationship between coronary slow flow (CSF) and coronary sinus (CS) reflux has not been previously studied. This study aimed to investigate the relationship between CSF and CS reflux and Thebesian valve presence as well as the relationship between CS reflux and serum annexin-V and ICAM-1 levels. METHODS: In this case-control study, patients were divided into two groups: CSF (n = 13) and control (n = 7) groups. CS flow parameters and Thebesian valve presence were evaluated by cardiac magnetic resonance (CMR). Moreover, serum ICAM-1 and annexin-V levels were measured. RESULTS: Regurgitation volume and regurgitation fraction, indicators of reflux flow in CS, were higher in the CSF group than in the control group (p = 0.039 and p = 0.019). Fewer Thebesian valves were observed in the CSF group than in the control group (p = 0.022). Furthermore, a positive correlation was found between regurgitation volume and regurgitation fraction and serum annexin-V and ICAM-1 levels (r = 0.813, p < 0.001 and r = 0.996, p < 0.001; r = 0.817, p < 0.001 and r = 0.993, p < 0.001, respectively). CONCLUSIONS: This study revealed the significant relationship between CSF and reflux flow in CS. The fact that the patients in the CSF group have fewer Thebesian valves suggests the importance of the valve in preventing backward flow from the coronary vein. A positive correlation between serum ICAM-1 and annexin-V levels with regurgitation volume and regurgitation fraction indicates that after a certain threshold, CS reflux should be considered an abnormal condition.

Clinical characteristics and in-hospital outcomes of acute decompensated heart failure patients with and without atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) and heart failure (HF) are common cardiovascular diseases. The impact of AF on in-hospital outcomes in acute decompensated heart failure (ADHF) is controversial. The aim of this study is to determine the prevalence of AF among hospitalized patients with ADHF and describe the clinical characteristics and in-hospital outcomes of these patients with and without AF. METHODS: We examined the multicenter, observational data from the real-life data of hospitalized patients with HF: Journey HF-TR study in Turkey that studied the clinical characteristics and in-hospital outcomes of hospitalized patients with ADHF between September 2015 and September 2016. RESULTS: Of the 1,606 patients hospitalized with ADHF, 626 (39%) had a history of AF or developed new-onset AF during hospitalization. The patients with AF were older (71±12 vs. 65±13 years; p<0.001) and more likely to have a history of hypertension, valvular heart disease, and stroke. The AF patients were less likely to have coronary artery disease and diabetes. In-hospital adverse event rates and length of in-hospital stay were similar in ADHF patients, both with and without AF. In-hospital all-cause mortality rate was higher in patients with AF than in patients without AF, although the difference was not statistically significant (8.9% vs. 6.8%; p=0.121). CONCLUSION: AF has been found in more than one-third of the patients hospitalized with ADHF, and it has varied clinical features and comorbidities. The presence of AF is not associated with increased adverse events or all-cause mortality during the hospitalization time.

Is the Increased Septal Perfusion the Signal of Asymmetrical Septal Hypertrophy?

In this study, we have compared scintigraphic and echocardiographic data in order to investigate whether increased septal perfusion represents asymmetrical septal hypertrophy (ASH), which is a symptom followed in the scintigraphy of myocardial perfusion. The study consists of a total of 186 patients (120 females and 66 males with an average age of 59.45 ± 11.54 years) who had normal myocardial perfusion scintigraphy and echocardiography examinations. Statistical comparison of septal wall thickness measurements obtained from echocardiography and septal-to-lateral wall ratios (S/L ratio) was performed scintigraphically. Left ventricular mass values were obtained as both scintigraphic and echocardiographic data and their correlations were evaluated in order to assess the presence of left ventricular hypertrophy (LVH). In statistical analyses, the values of interventricular septal thickness in diastole (IVSd), left ventricle posterior wall thickness in diastole (LVPWd), left ventricle mass (LVM), and left ventricle mass index (LVMI) were found to be significantly higher in group 2 (S/L ratio >1) compared to group 1 (S/L ratio <1). In addition, S/L ratio is significantly correlated with echocardiographic IVSd, LVPWd, LVM, LVMI, and scintigraphic LVM (rest) values. Furthermore, echocardiographic LVM and LVMI values were significantly correlated with LVM and LVMI values obtained from scintigraphy. It should be known that increased S/L ratio that can be monitored during scintigraphic studies can be an indicator of septal hypertrophy and/or LVH, however, further examination and close follow-ups should be performed in necessary cases.

Epicardial Adipose Tissue Is Increased in Patients With Inflammatory Bowel Disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) have high cardiovascular morbidity, and, in general, epicardial adipose tissue thickness is related to atherosclerotic vascular disease. This study aimed to investigate the association between epicardial adipose tissue thickness and carotid intima-media thickness as markers of early atherosclerosis in patients with IBD. METHODS: The study comprised 47 patients with IBD (25 with Crohn disease and 22 with ulcerative colitis) and 35 control participants. In all individuals, epicardial adipose tissue and carotid intima-media thickness values were measured by sonography. RESULTS: The mean age ± SD of the 47 patients with IBD was 42.3 ± 11.2 years, versus 41.4 ± 10.1 years for the control group. The epicardial adipose tissue thickness was higher in both the Crohn disease and ulcerative colitis groups compared to the control group (P < .001), but not the carotid intima-media thickness (P = .695 and .917, respectively). There was a strong positive correlation between the carotid intima-media and epicardial adipose tissue thickness values in the Crohn disease and ulcerative colitis groups (r = 0.757; 95% confidence interval, 0.711-0.901; r = 0.786; 95% confidence interval, 0.364-0.615; both P < .001). However, there was no significant difference between the patients who were in the active and inactive disease periods in both groups in terms of carotid intima-media and epicardial adipose tissue thickness values. CONCLUSIONS: Our findings suggest that epicardial adipose tissue thickness might be a marker for detection of early atherosclerosis in patients with IBD. There was a strong positive correlation between carotid intima-media thickness and epicardial adipose tissue thickness values in the patients with IBD. However, there was no correlation between IBD activity and carotid intima-media or epicardial adipose tissue thickness.

Assessment of the effects of frequent ventricular extrasystoles on the left ventricle using speckle tracking echocardiography in apparently normal hearts.

OBJECTIVE: Impairment in left ventricular (LV) function due to excessive ventricular extrasystoles (VESs) occurs during long-time follow-up. Speckle tracking echocardiography (STE) has been shown to be superior to conventional methods for evaluating cardiac functions. We aimed to use STE for early detection of LV dysfunction in patients with apparently normal hearts who have frequent VESs. METHODS: Fifty-five patients with frequent VESs were identified according to the Lown classification (Grade 2; unifocal more than 30 times in 1 h). Subjects aged 22-60 years with frequent VESs that had been detected for at least 1 year were included in the study according to the inclusion criteria. Forty-five subjects with similar demographic characteristics, but without VESs, were included as the control group. All participants were evaluated by STE. RESULTS: Fifty-five patients with frequent VESs (mean age 47 years, range 22-60 years; 42.2% male) and 45 control subjects (mean age 46 years, range 22-60 years; 37.8% male) were enrolled in the study. Global LV longitudinal strain (GLS) was decreased in patients with frequent VESs (-18.41±3.37 and -21.82±2.43; p<0.001). In addition, global LV circumferential strain was decreased in patients with frequent VESs (-16.83±6.06, -20.51±6.02; p<0.001). The frequency and exposure time of VESs were negatively correlated with GLS (r=-0.398, p<0.001; r=-0.191, p=0.001, respectively). CONCLUSION: STE revealed that LV functions were decreased in patients with VESs. This deterioration increased with the frequency and exposure time of VESs. Impairment of LV function due to excessive VESs occurs during long-time follow-up. STE may be used for early detection of LV dysfunction.

Atrial conduction time, and left atrial mechanical and electromechanical functions in patients with polycystic ovary syndrome: interatrial conduction delay.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of women during the reproductive period. Cardiovascular risk factors are more frequent in patients with PCOS. We aimed to investigate the P-wave dispersion (Pd), inter- and intra-atrial conduction time and mechanical functions of the left atrium (LA) in patients with PCOS. METHODS: Forty-eight patients with PCOS and 38 normal healthy women were enrolled in this study. A 12-lead surface electrocardiogram was used to evaluate Pd. Left ventricular (LV) functions were measured using conventional and tissue Doppler imaging (TDI) methods. Inter- and intra-atrial conduction times were measured by TDI. LA volumes were measured echocardiographically with the biplane area-length method from the apical four-chamber view. RESULTS: Heart rate (82.02 ± 13.15 vs 74.24 ± 11.02 bpm, p = 0.014) and Pd were significantly increased in the PCOS patients [27 ± 5 vs 24 ± 6 ms, p = 0.035]. Transmitral E/A ratio was significantly lower in the PCOS patients than in the controls (1.5 ± 0.3 vs 1.7 ± 0.4 m/s, p = 0.023). Passive emptying volume (12.54 ± 4.39 vs 15.28 ± 3.85 ml/m(2), p = 0.004) and passive emptying fraction [54.4 (21-69) vs 59.1% (28-74), p = 0.008] were significantly decreased in PCOS patients. Total emptying volume was significantly decreased (17.9 ± 5.49 vs 20.67 ± 4.29 ml/m(2), p = 0.018) in PCOS patients. Interatrial (19 ± 7.4 vs 15 ± 6.4 ms, p = 0.035) and intra-atrial [8.5 (1-19) vs 5 ms (1-20), p = 0.026] electromechanical delays were found to be significantly higher in PCOS patients. CONCLUSION: This study showed that patients with PCOS had increased inter- and intra-atrial conduction delays, and decreased LA passive emptying volumes and fractions.

Right ventricular function and its relationship with grade of hepatosteatosis in non-alcoholic fatty liver disease.

OBJECTIVE: This study was designed to assess right ventricular systolic and diastolic function and its relationship with grade of hepatosteatosis (HS) in non-alcoholic fatty liver disease (NAFLD) patients using conventional and tissue Doppler echocardiography. METHODS: NAFLD was diagnosed in 32 individuals (15 males, 17 females; 59% were grade I HS, 41% grade II-III HS) by means of ultrasonography. Twenty-two individuals, whose ultrasonography data did not show HS, comprised the control group (11 males, 11 females) and were included in the study. Right ventricular systolic and diastolic function and their relationship with grade of HS were assessed by conventional and tissue Doppler echocardiography. Additionally, right ventricular global function was assessed by myocardial performance index (MPI). RESULTS: When compared by conventional echocardiographic parameters, there were no significant differences between the two groups. With tissue Doppler parameters, the tricuspid annulus peak early diastolic velocity and ratio of early-to-late diastolic velocity were lower in the patients than in the controls (p = 0.03, p = 0.02, respectively). The isovolumetric relaxation time and MPI were significantly higher (p < 0.001, p < 0.001, respectively) in the patient group. HS grade was positively correlated with right ventricular isovolumetric relaxation time and MPI index (r = 0.295, p = 0.03, r = 0.641, p < 0.001, respectively). CONCLUSION: These results show that right ventricular diastolic dysfunction (RVDD) in patients with NAFLD and degree of HS was associated with RVDD.