Current barriers and recommendations on the diagnosis of transthyretin amyloid cardiomyopathy: a Delphi study.

Objectives: This study has been conducted to investigate the non-invasive diagnostic journey of patients with a transthyretin amyloid cardiomyopathy (aTTR-CM) in Turkey, identify the challenges and uncertainties encountered on the path to diagnosis from the perspectives of expert physicians, and develop recommendations that can be applied in such cases. Methods: This study employed a three-round modified Delphi method and included 10 cardiologists and five nuclear medicine specialists. Two hematologists also shared their expert opinions on the survey results related to hematological tests during a final face-to-face discussion. A consensus was reached when 80% or more of the panel members marked the "agree/strongly agree" or "disagree/strongly disagree" option. Results: The panelists unanimously agreed that the aTTR-CM diagnosis could be established through scintigraphy (using either 99mTc-PYP, 99mTc-DPD, or 99mTc-HMPD) in a patient with suspected cardiac amyloidosis (CA) without a further investigation if AL amyloidosis is ruled out (by sFLC, SPIE and UPIE). In addition, scintigraphy imaging performed by SPECT or SPECT-CT should reveal a myocardial uptake of Grade ≥2 with a heart-to-contralateral (H/CL) ratio of ≥1.5. The cardiology panelists recommended using cardiovascular magnetic resonance (CMR) and a detailed echocardiographic scoring as a last resort before considering an endomyocardial biopsy in patients with suspected CA whose scintigraphy results were discordant/inconclusive or negative but still carried a high clinical suspicion of aTTR-CM. Conclusion: The diagnostic approach for aTTR-CM should be customized based on the availability of diagnostic tools/methods in each expert clinic to achieve a timely and definitive diagnosis.

Can lipid mediators and free fatty acids guide acute coronary syndrome diagnosis and treatment?

OBJECTIVE: The aim of this study was to investigate fatty acids, lipid mediator levels, and the desaturase index rates on different acute coronary syndrome types and their possible relationship with routine lipid parameters. METHODS: The study included 81 patients with myocardial infarction (MI), 20 patients with unstable angina pectoris, and 31 healthy people. Fatty acids, CD59, lipoxin A4, 8-isoprostane, serum lipids, albumin, C-reactive protein (CRP), and high sensitive troponin levels were measured in all participants. RESULTS: When the fatty acid groups were evaluated as a ratio of albumin, MUFA/albumin and SFA/albumin ratios were significantly higher in the MI group compared to the control group. Although CD59 and lipoxin A4 levels were higher in the control group, there was no significant differences between the groups. When lipoxin A4/CRP and CD59/CRP ratios were evaluated, the results were significantly lower than those in the control group. CONCLUSION: Lipid mediators may be useful in treating atherosclerosis by contributing to the resolution of inflammation.

Unusual Case of Pulmonary Hypertension due to Acquired Arteriovenous Fistula.

Pulmonary hypertension is a disease process affecting pulmonary circulation and is defined by an increase in pulmonary artery pressure subsequently causing right ventricular failure. Vascular complications, including arteriovenous (AV) fistula, are recognized, but are uncommon complications of spinal surgery. AV fistula increases venous return to the right heart and can promote a volume overload related high-output cardiac state, pulmonary hypertension, and right heart failure. Hereby, we describe a rare pulmonary hypertension case with severe right heart failure, lower leg edema, and progressive dyspnea caused by an AV fistula between the left common iliac artery and vein as a complication of a lumbar spinal/disk surgery. Pulmonary hypertension was confirmed by hemodynamic assessments and the etiology was established by both abdominal computed tomography and conventional peripheric angiography. After closure of the AV-fistula by stent-graft implantation, the right heart failure resolved completely.

Six-Minute Walk Test: How to do Guide for Performing a Reliable Test, Interpretation, and Prognostication in Pulmonary Hypertension.

Six-minute walk test (6MWT) is the most widely used exercise capacity measurement worldwide in patients with pulmonary hypertension (PH). Although cardiopulmonary exercise testing (CPET) is the gold standard for the assessment of exercise capacity in cardiovascular diseases; the limited accessibility of the device, the need for experience in interpreting the results, and the difficulties in performing CPET in advanced PH have aroused the interest in the application of easier methods for the measurement of exercise capacity. Since then, accumulated data proved that; 6-minutes walking distance (6MWD) can be used to determine exercise capacity and is highly correlated with maximum oxygen consumption (peak VO2) detected by CPET in patients with heart failure and/or PH. Moreover, 6MWT is very easy and practical to apply in all PH subgroups. This review is focused on the application of a reliable 6MWT and the interpretation of the results in patients with PH.

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.

Risk Assessment Tool Implementation in Congenital Heart Disease-Associated Pulmonary Arterial Hypertension.

BACKGROUND: Risk assessment is recommended for patients with congenital heart disease-associated pulmonary arterial hypertension. This study aims to compare an abbreviated version of the risk assessment strategy, noninvasive French model, and an abridged version of the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management 2.0 risk score calculator, Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2. METHODS: We enrolled a mixed prevalent and incident cohort of patients with congenital heart disease-associated pulmonary arterial hypertension (n = 126). Noninvasive French model comprising World Health Organization functional class, 6-minute walk distance, and N-terminal pro-hormone of brain natriuretic peptide or brain natriuretic peptide was used. Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2 includes functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide/N-terminal pro-hormone of brain natriuretic peptide, and estimated glomerular filtration rate. RESULTS: The mean age was 32.17 ± 16.3 years. The mean follow-up was 99.41 ± 58.2 months. Thirty-two patients died during follow-up period. Most patients were Eisenmenger syndrome (31%) and simple defects (29.4%). Most patients received monotherapy (76.2%). Most patients were World Health Organization functional class I-II (66.6%). Both models effectively identified risk in our cohort (P =.0001). Patients achieving 2 or 3 noninva-sive low-risk criteria or low-risk category by Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2 at follow-up had a significantly reduced risk of death. Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2 approximates noninvasive French model at discriminating among patients based on c-index. Age, high risk by Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management Lite 2, and the presence of 2 or 3 low-risk criteria by noninvasive French model emerged as an independent predictors of mortality (multivariate hazard ratio: 1.031, 95% CI: 1.005-1.058, P =.02; hazard ratio: 4.258, CI: 1.143-15.860, P =.031; hazard ratio: 0.095, CI: 0.013-0.672, P =.018, respectively). CONCLUSIONS: Both abbreviated risk assessment tools may provide a simplified and robust method of risk assessment for congenital heart disease-associated pulmonary arterial hypertension. Patients not achieving low risk at follow-up may benefit from aggressive use of available therapies.

Current clinical practice of cardiac resynchronization therapy in Turkey: Reflections from Cardiac Resynchronization Therapy Survey-II.

OBJECTIVE: Cardiac resynchronization therapy (CRT) has been shown to reduce mortality in selected patients with heart failure with reduced ejection fraction (HFrEF). CRT Survey-II was a snapshot survey to assess current clinical practice with regard to CRT. Herein, we aimed to compare Turkish data with other countries of European Society of Cardiology (ESC). METHODS: The survey was conducted between October 2015 and December 2016 in 42 ESC member countries. All consecutive patients who underwent a de novo CRT implantation or a CRT upgrade were eligible. RESULTS: A total of 288 centers included 11,088 patients. From Turkey, 16 centers recruited 424 patients representing 12.9% of all implantations. Compared to the entire cohort, Turkish patients were younger with a lower proportion of men and a higher proportion with ischemic etiology. Electrocardiography (ECG) showed sinus rhythm in 81.5%, a QRS duration of <130 ms in 10.1%, and ≥150 ms in 63.8% of patients. Left bundle branch block (LBBB) was more common. Median left ventricular ejection fraction (LVEF) was 25%, lower than in the overall ESC cohort, but NYHA class was more often II. Most common indication for CRT implantation was HF with a wide QRS (70.8%). Almost 98.3% of devices implanted were CRT-D, in contrast to the overall cohort. Fluoroscopy time was longer, but duration of overall procedure was shorter. LV lead implantation was unsuccessful in 2.6% patients. Periprocedural complication rate was 6.3%. The most common complication was bleeding. Remote monitoring was less utilized. CONCLUSION: These are the first observational data reflecting the current CRT practice in Turkey and comparing it with other countries of Europe. Findings of this study may help detect gaps and provide insights for improvement.

Concealed role of red blood cells in pathogenesis of pulmonary arterial hypertension: Decreased red blood cell nitric oxide generation and effect of Rho-Kinase inhibitor fasudil.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease characterized with alterations in pulmonary vasculature yielding increased pulmonary arterial resistance. Emerging evidences suggest important regulatory roles of red blood cells (RBCs) on nitric oxide (NO) bioavailability, mainly by modulating their endothelial nitric oxide synthase (eNOS) enzyme activity. OBJECTIVE: The aim of this pilot study was to evaluate the alterations in RBC eNOS activity and intracellular NO generation in PAH patients and the modulatory effects of Rho-Kinase (ROCK) inhibitors. METHODS: RBCs were isolated from patients with PAH and age-matched healthy subjects and were analyzed for their eNOS activity and NO generation capacity under the conditions of the presence or absence of ROCK inhibitor, fasudil. Phosphotidylserine (PS) exposure was also defined. RESULTS: eNOS activity and intracellular NO generation were lower in RBC from PAH patients. ROCK inhibitor increased basal eNOS activity and improved NO generation capacity of RBC of PAH patients to healthy control levels. PS exposure levels were also higher in RBC of PAH patients. CONCLUSIONS: This study provides first evidences for decreased RBC eNOS activity due to its ROCK mediated negative regulation in PAH patients. Considering increased ROCK activity contribution to progression of PAH, ROCK inhibition influences NO bioavailability through RBC eNOS, in addition to endothelial eNOS.

Risk assessment and survival of patients with pulmonary hypertension: Multicenter experience in Turkey.

OBJECTIVE: Risk stratification continues to evolve in pulmonary arterial hypertension (PAH). Our aim was to further confirm the risk assessment strategy in our cohort and to determine the most reliable model. METHODS: We enrolled incident patients with idiopathic PAH (IPAH), heritable, drug-induced, congenital heart disease (CHD), connective tissue diseases (CTD) subsets, and chronic thromboembolic pulmonary hypertension (CTEPH) from January 2008 to February 2018. Data from the baseline and subsequent follow-ups within 1 year of diagnosis were included. An abbreviated risk assessment strategy was applied using the following variables: functional class (FC), 6-minute walk distance (6 MWD), N-terminal pro-brain natriuretic peptide (NT-proBNP) or BNP, right atrial (RA) area, pericardial effusion, the mean RA pressure, cardiac index, and mixed venous oxygen saturation. Three different methods were applied to categorize patients. RESULTS: A total of 189 subjects (46+-17 years, 23% male) were included. Sixty-one patients had died. The survival differed significantly between the risk groups both at diagnosis and during the follow-up. Patients with a low-risk profile had a better survival rate. An abbreviated risk assessment tool predicted mortality at early follow-up in the entire group and CHD, CTD subsets, and CTEPH, separately. An overall mortality among risk categories was significantly different according to each categorization method. The most reliable model comprised FC, 6 MWD, NT pro-BNP/BNP, and the RA area at the follow-up. CONCLUSION: The abbreviated risk assessment tool may be valid for the PAH subsets and CTEPH. Echocardiographic variables do matter. A model comprising FC, 6 MWD, NT pro-BNP/BNP, and the RA area at the follow-up could be useful for better prognostication.

Assessment of left atrial function using speckle tracking echocardiography in ankylosing spondylitis: a case-control study.

The aim of this study is to assess the left atrium (LA) deformation parameters by using 2D speckle tracking echocardiography (2D-STE) in ankylosing spondylitis (AS) patients and to evaluate the relationship between these parameters and AS clinical indexes. 30 patients with AS (22 males, 8 females) and 30 healthy individuals (19 males, 11 females) were enrolled in this study. Transthoracic echocardiography was performed to both groups. Besides the conventional echocardiographic parameters, the LA strain parameters; including systolic-reservoir (LA S-S), early diastolic-conduit (LA S-E), late diastolic-contraction (LA S-A) were measured. No significant difference was found between two groups in terms of conventional echocardiographic parameters except mean deceleration time (DT). Mean DT was prolonged in the AS patients compare with the control group (173.5 ± 22.5 vs. 155.3 ± 36.7, p = 0.025). In the AS patients, LA S-S (48.3 ± 9.4 vs. 56.9 ± 10.1, p = 0.001), LA S-E (26.4 ± 6.4 vs. 31.6 ± 7.3, p = 0.005) and LA S-A (21.9 ± 4.7 vs. 25.4 ± 5.7, p = 0.013) values were statistically lower than the control group. Also a negative correlation was observed between the Bath Ankylosing Spondylitis Metrology Index (BASMI) and LA S-S (r = - 0.509, p = 0.004), LA S-E (r = - 0.501, p = 0.005). Our study demonstrated that 2D-STE is a useful method to determine the left atrial involvement in AS patients without the clinical evident of cardiovascular disease.

Evaluation of cardiac autonomic functions in myasthenia gravis.

OBJECTIVE: We aimed to comprehensively evaluate cardiac autonomic function in patients with MG and to investigate the relationship between this disorder and disease duration, thymoma and acetylcholine receptor antibody positivity in cases of cardiac autonomic disorder. METHODS: The study included 30 patients with MG and 30 age-matched healthy control subjects. Haemodynamic parameters (heart rate, systolic and diastolic blood pressure) and autonomic parameters (low frequency [LF], high-frequency [HF], sympathovagal balance [LF/HF], baroreceptor reflex sensitivity [BRS]) of the patients were automatically measured at rest and in a tilted position with the Task Force Monitor. RESULTS: The mean systolic and diastolic blood pressure measurements obtained at rest and during the tilt test were higher in patients with MG. Sympathovagal balance has been disturbed in favour of sympathetic tone, and parasympathetic insufficiency has become more prominent. When baroreceptor sensitivity was used as the second parameter to evaluate autonomic heart functions, BRS at rest and during the tilt test was lower in the MG group compared with the control group. DISCUSSION: These results suggest that sympathovagal balance has been disturbed in favour of sympathetic tone and that parasympathetic insufficiency has become more prominent. The current findings support the presence of cardiac autonomic involvement in patients with MG. The determination of cardiac autonomic function via noninvasive methods among patients with MG has high predictive value. The identification of autonomic dysfunction at an early stage and the early treatment of cardiovascular diseases can reduce morbidity and mortality.

Right atrial thrombus associated with subclavian catheter developed due to total parenteral nutrition application.

Central venous catheterization as a frequent routine clinical procedure may have significant complications. Mechanical complications may occur during catheter placement, whereas thromboembolic and infectious complications can be seen during follow-up. Total parenteral nutrition (TPN) associated central venous catheterizations may result in early mechanical complications and thrombotic and infectious complications in the long term. This paper describes a patient diagnosed as mitochondrial neurogastrointestinal encephalomyopathy requiring long-term central venous catheterization for TPN implementation, who had an infected thrombus on the catheter tip resected by cardiac surgery.

Determination of subclinical atherosclerosis in plaque type psoriasis patients without traditional risk factors for atherosclerosis.

OBJECTIVES: Systemic inflammation plays an important role in the pathogenesis of atherosclerosis in psoriasis patients. Therefore, persistent skin inflammation in psoriasis patients may contribute to the development of premature atherosclerosis, as it occurs in rheumatoid arthritis and systemic lupus erythematosus. We aimed to evaluate the relationship between subclinical atherosclerosis and psoriasis by using pulse wave velocity (PWV) and the measurement of carotid intima media thickness (CIMT) in psoriatic patients. STUDY DESIGN: Fifty-seven plaque-type psoriasis patients (31 males, 26 females; mean age 41±10.8 years) and 60 healthy individuals (32 males, 28 females; mean age 40±9.4 years) were included. Atherosclerotic risk factors were excluded in both of the groups. Demographic, bio-chemical data, psoriasis area and severity index (PASI) score of the psoriasis group, and disease duration were recorded. Carotid-femoral artery PWV and CIMT values were compared. RESULTS: PWV, and the maximum and average CIMT values of psoriasis patients were higher than those of the healthy group (PWV: 7.04±1.1 m/sn vs. 6.03±0.61 m/sn, p<0.001; maximum CIMT: 0.86±0.09 mm vs. 0.77±0.06 mm, p<0.001; mean CIMT: 0.73±0.09 mm vs. 0.66±0.06 mm p<0.001, respectively). Although there was no difference in the lipid levels of the groups, total/HDL cholesterol (4.40±1.26 vs. 3.88±1.18, p=0.02, respectively), and LDL/HDL cholesterol ratios (2.78±0.98 vs. 2.32±0.92, p=0.01, respectively) of the psoriasis group were higher than those of the healthy group. A positive correlation was observed between PASI and the PWV (r=0.417, p=0.001). CONCLUSION: Despite the nonexistence of atherosclerotic risk factors, the risk of development of atherosclerosis is higher in psoriasis patients compared to healthy individuals. In addition to damage of the artery wall caused by systemic inflammation, lipid metabolism disorders may contribute to the development of atherosclerosis in these patients.

Successful percutaneous epicardial ablation of an accessory pathway located at the right atrial appendage.

In patients with Wolff-Parkinson-White syndrome, difficulty in ablation of accessory pathways is associated with failures and recurrences. Epicardially located accessory pathways may require different management strategies when conventional ablation attempts fail. In particular, an epicardial accessory pathway communicating the right atrial appendage to the right ventricle is an extraordinary situation resulting in difficulties in ablation. Hereby, we report on a challenging case of percutaneous epicardial ablation of an epicardial accessory pathway located at right atrial appendage in a 28-year-old man with Wolff-Parkinson-White syndrome, who had a prior history of unsuccessful endocardial ablation. Percutaneous epicardial ablation may be a viable option obviating the necessity of surgical ablation procedures for difficult ablation cases with epicardial accessory pathways.