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.

The Frequency of Fabry Disease in Patients with Cardiac Hypertrophy of Various Phenotypes Including Prominent Papillary Muscle: The TUCARFAB Study in Turkey.

BACKGROUND: The present study aimed to identify the frequency of Fabry disease in patients with cardiac hypertrophy of unknown etiology and to evaluate demographic and clinical characteristics, enzyme activity levels, and genetic mutations at the time of diagnosis. METHODS: This national, multicenter, cross-sectional, single-arm, observational registry study was conducted in adult patients with a clinical echocardiographic diagnosis of left ventricular hypertrophy and/or the presence of prominent papillary muscle. In both genders, genetic analysis was performed by DNA Sanger sequence analysis. RESULTS: A total of 406 patients with left ventricular hypertrophy of unknown origin were included. Of the patients, 19.5% had decreased enzyme activity (≤2.5 nmol/mL/h). Although genetic analysis revealed GLA (galactosidase alpha) gene mutation in only 2  patients (0.5%), these patients were considered to have probable but not 'definite Fabry disease' due to normal lyso Gb3 levels and gene mutations categorized as variants of unknown significance. CONCLUSION: The prevalence of Fabry disease varies according to the characteristics of the population screened and the definition of the disease used in these trials. From cardiology perspective, left ventricular hypertrophy is the major reason to consider screening for Fabry disease. Enzyme testing, genetic analysis, substrate analysis, histopathological examination, and family screening should be performed, when necessary, for a definite diagnosis of Fabry disease. The results of this study underline the importance of the comprehensive use of these diagnostic tools to reach a definite diagnosis. The diagnosis and management of Fabry disease should not be based solely on the results of the screening tests.

[Fabry disease in cardiology: Diagnosis and therapeutic approaches]. / Kardiyolojide Fabry hastaligi: Tani ve tedavi yaklasimlari.

Fabry disease is a rare, progressive, X-linked inherited storage disorder due to absent or deficient of lysosomal alfa galactosidase A activity. Deficient activity of alfa-galactosidase A results in progressive accumulation of globotriaosylceramide in a variety of tissues and organs including myocardium, kidney and nerve system. This disorder predominantly affects males; however, female heterozygotes may also be affected with a less severe clinical picture. Classic Fabry disease is usually diagnosed in early age of childhood because of multiorgan involvement whereas cardiac and renal variants of Fabry are manifested in 30-50 years of age because of late onset of clinical picture in which other organs involvement are uncommon. Although Fabry is known as a very rare disease, its prevalence is reported to be higher in patients with ventricular hypertrophy, chronic kidney disease and cryptogenic stroke. From the cardiology point of view, the most important key finding of the disease is unexplained ventricular hypertrophy. However, in clinical practice, ventricular hypertrophy is usually thought to be due to hypertrophic cardiomyopathy in the absence of hypertension or aortic stenosis and Fabry disease is often undiagnosed or overlooked. Early diagnosis and enzyme replacement therapy have been shown to significantly improve prognosis. The aim of this paper is to provide a comprehensive review including epidemiology, prognosis, clinical presentation, diagnosis and therapeutic approaches of cardiac variant of Fabry based on the available data in the literature.

Cardiac amyloidosis: Recent advances in the diagnosis and therapy.

Cardiac amyloidosis (CA) is a progressive cardiomyopathy in which misfolded endogenous proteins form amyloid fibrils that deposit in the heart as well as kidneys, liver, gastrointestinal tract and soft tissues. The most common forms of CA include immunoglobulin light chain (AL) amyloidosis and transthyretin (TTR) amyloidosis. Although cardiac amyloidosis is thought to be a very rare disease, emerging data suggested that 13% of heart failure patients with preserved ejection fraction and 16-26% of advanced aged patients with severe aortic stenosis may have TTR-CA. Amyloidosis with cardiac involvement shows poor prognosis with a median survival of 6 months in AL-CA and 26-43 months in TTR-CA. Early diagnosis and novel therapeutic options have been shown to significantly improve prognosis. Recent diagnostic techniques such as cardiac MR or nuclear scintigraphy using bone isotopes as well as increasingly wide use of echocardiography, genetic testing, biopsy and histopathological analysis allow the clinicians to make early diagnosis of CA. The aim of this paper is to provide a comprehensive review including etiology, clinical presentation, diagnosis and management of CA and to address recent important advances in noninvasive cardiac imaging techniques and novel therapeutic approaches based on the available data in the literature.

Is there a gender gap in secondary prevention of coronary artery disease in Turkey?

OBJECTIVE: It has been reported that women receive fewer preventive recommendations regarding pharmacological treatment, lifestyle modifications, and cardiac rehabilitation compared with men who have a similar risk profile. This study was an investigation of the impact of gender on cardiovascular risk profile and secondary prevention measures for coronary artery disease (CAD) in the Turkish population. METHODS: Statistical analyses were based on the European Action on Secondary and Primary Prevention through Intervention to Reduce Events (EUROASPIRE)-IV cross-sectional survey data obtained from 17 centers in Turkey. Male and female patients, aged 18 to 80 years, who were hospitalized for a first or recurrent coronary event (coronary artery bypass graft, percutaneous coronary intervention, acute myocardial infarction, or acute myocardial ischemia) were eligible. RESULTS: A total of 88 (19.7%) females and 358 males (80.3%) were included. At the time of the index event, the females were significantly older (p=0.003) and had received less formal education (p<0.001). Non-smoking status (p<0.001) and higher levels of depression and anxiety (both p<0.001) were more common in the female patients. At the time of the interview, conducted between 6 and 36 months after the index event, central obesity (p<0.001) and obesity (p=0.004) were significantly more common in females. LDL-C, HDL-C or HbA1c levels did not differ significantly between genders. The fasting blood glucose level was significantly higher (p=0.003) and hypertension was more common in females (p=0.001). There was no significant difference in an increase in physical activity or weight loss after the index event between genders, and there was no significant difference between genders regarding continuity of antiplatelet, statin, beta blocker or ACEi/ARB II receptor blocker usage (p>0.05). CONCLUSION: Achievement of ideal body weight, fasting blood glucose and blood pressure targets was lower in women despite similar reported medication use. This highlights the importance of the implementation of lifestyle measures and adherence to medications in women.

[EUROASPIRE-IV: European Society of Cardiology study of lifestyle, risk factors, and treatment approaches in patients with coronary artery disease: Data from Turkey]. / EUROASPIRE-IV: Avrupa Kardiyoloji Dernegi'nin koroner arter hastalarinda yasam tarzi, risk faktörleri ve tedavi yaklasimi üzerine çalismasi: Türkiye verileri.

OBJECTIVE: Data from EUROASPIRE-IV Turkey report investigating risk factors and adherence to guidelines in patients hospitalized for coronary artery disease are presented and results are compared with those of EUROASPIRE-III Turkey and EUROASPIRE-IV Europe. METHODS: Study was performed in 24 European countries, including Turkey (17 centers). Patients (18-80 years old) hospitalized for coronary (index) event during preceding 3 years were identified from hospital records and interviewed ≥6 months later. Patient information regarding index event was acquired from hospital records. Anamnesis was obtained during the interview, and physical examination and laboratory analyses were performed. RESULTS: Median age at the index coronary event was 58.8 years, and it was significantly decreased compared with last EUROASPIRE-III study (60.5 years), which was conducted at the same centers 6 years earlier (p=0.017). Of all patients, 19.3% were under 50 years of age and mean age was lower than that of EUROASPIRE-IV Europe (62.5 years). Comparing EUROASPIRE-IV Turkey with EUROASPIRE-III Turkey, rate of smokers increased to 25.5% from 23.1% (p=0.499), obesity increased to 40.7% from 35.5% (p=0.211), total cholesterol level increased to 49.6% from 48.3% (p=0.767), and diabetes rate increased to 39.7% from 33.6% (p=0.139), however none of the differences reached a level of statistical significance. Only 11.7% of the smokers quit after coronary event. Rates for these factors were lower in EUROASPIRE-IV Europe (16% for smoking, 37.6% for obesity, and 26.8% for diabetes). CONCLUSION: EUROASPIRE-IV Turkey data revealed that secondary prevention was unsatisfactory and had progressed unfavorably compared with last EUROASPIRE study, some risk factors were more uncontrolled than overall European average, and coronary artery events at young age remain an important problem.

OPERATOR DEPENDENCY OF THE RADIATION EXPOSURE IN CARDIAC INTERVENTIONS: FEASIBILITY OF ULTRA LOW DOSE LEVELS.

INTRODUCTION: Mean radiation exposure in invasive cardiology varies greatly between different centres and interventionists. The International Commission on Radiological Protection and the EURATOM Council stipulate that, despite reference values, 'All medical exposure for radiodiagnostic purposes shall be kept as low as reasonably achievable' (ALARA). The purpose of this study is to establish the effects of the routine application of ALARA principles and to determine operator and procedure impact on radiation exposure in interventional cardiology. MATERIALS AND METHODS: A total of 240 consecutive cardiac interventional procedures were analysed. Five operators performed the procedures, two of whom were working in accordance with ALARA principles (Group 1 operators) with the remaining three working in a standard manner (Group 2 operators). Radiation exposure levels of these two groups were compared. RESULTS: Total fluoroscopy time and the number of radiographic runs were similar between groups. However, dose area product and cumulative dose were significantly lower in Group 1 when compared with Group 2. Radiation levels of Group 1 were far below even the reference levels in the literature, thus representing an ultra-low-dose radiation exposure in interventional cardiology. CONCLUSION: By use of simple radiation reducing techniques, ultra-low-dose radiation exposure is feasible in interventional cardiology. Achievability of such levels depends greatly on operator awareness, desire, knowledge and experience of radiation protection.

Severe tricuspid regurgitation mimicking constrictive pericarditis.

PATIENT: Female, 62 FINAL DIAGNOSIS: Tricuspid regurgitation Symptoms: Dyspnea exertional • fatigue • leg edema MEDICATION: - Clinical Procedure: - Specialty: Cardiology. OBJECTIVE: Challenging differential diagnosis. BACKGROUND: Tricuspid regurgitation (TR) can mimic some hemodynamic findings of constrictive pericarditis (CP), due to the restraining effect of the enlarged right heart on intact pericardium and on the left ventricle. In this article, we report a case of severe tricuspid regurgitation in which hemodynamic findings were consistent with CP. CASE REPORT: A 62-year-old Caucasian woman presented with right heart failure symptoms. Echocardiography showed enlarged right heart chambers and severe tricuspid regurgitation. Right heart catheterization surprisingly demonstrated a constrictive physiology. Diastolic pressures of both ventricles were elevated and equalized, with a prominent deep and plateau pattern. The patient was re-evaluated with a further focus on constrictive pericarditis. However, echocardiography, thorax CT, and cardiac MRI did not demonstrate any pathological finding related to pericardium. The remaining explanation was that the severe TR itself and secondary right heart enlargement caused the restraining effect on the intact pericardium and on the left ventricle. The pericardium was normal and tricuspid annulus was severely dilated on surgical inspection. The tricuspid valve was replaced with a bioprosthetic valve. The patient did well just after the surgery, with a rapid decrease in cardiac pressures; however, she died due to respiratory failure on the 15(th) postoperative day. CONCLUSIONS: This was a case with right heart failure symptoms in which invasive hemodynamic findings were consistent with constrictive pericarditis and the noninvasive imaging modalities were not. This case illustrates that severe TR can mimic some hemodynamic findings of constrictive pericarditis, due to restraining effect of the enlarged right heart on intact pericardium and on the left ventricle. Lack of significant respiratory changes in hemodynamic parameters that can safely be demonstrated by echocardiography and cardiac MRI suggest a normal pericardium.

Diagnostic accuracy of mean platelet volume in prediction of clopidogrel resistance in patients with acute coronary syndrome.

OBJECTIVE: Clopidogrel therapy is the standard of care in patients with acute coronary syndrome (ACS) and stent implantation. However, concern arises because 25% of subjects are nonresponders to clopidogrel. As this nonresponsiveness is associated with increased adverse outcome, detection of these subjects in daily practice is important in order to withhold a more aggressive therapy and closer follow up. In this study we aimed to evaluate the relation between mean platelet volume (MPV) which is an indicator of platelet activation and clopidogrel nonresponsiveness. METHODS: The study was planned as a prospective cohort study. A total of 185 patients who had been on clopidogrel therapy for any acute coronary syndrome were enrolled in this study. Clopidogrel responsiveness was analyzed by Multiplate MP-0120 device by using the method of whole blood aggregometry. Blood samples were drawn 3.5 days after clopidogrel loading dose. The amount of ADP induced platelet aggregation was assessed as area under curve (AUC), and a cut-off value of 500, above which the patient is considered as clopidogrel nonresponder, was used. MPV was analyzed from the blood which were sampled at the admission of the patient by using automatic hemocounter. Independent sample t-test, ROC analyses and logistic regression analsis were used in statistical analysis. RESULTS: Among the 185 patients analyzed 41 were found to be clopidogrel nonresponder (22.1%). Mean MPV was found to be significantly higher in nonresponders compared to responders (8.7±0.82 fL vs. 8.1±0.83 fL, p<0.001). A cut-off value of 8.3 fL for MPV was detected in prediction of clopidogrel nonresponsiveness with a sensitivity of 76.6% and specificity of 68.3% (OR: 6.4; 95% CI 2.9-14.1, AUC: 0.70, p<0.001). CONCLUSION: This study showed that MPV can be used as a predictor of clopidogrel resistance in patients with ACS.

A mandatory modification in extracorporeal biventricular assist device (BIVAD) implantation: intercostal tunnel application: a case report.

In this case, our patient was a heart transplant candidate connected to a respiratory system. An extracorporeal biventricular assist device (BIVAD) was the only option in order to bridge to transplantation. In routine procedures, it is recommended that Berlin Heart Excor cannulas be removed through the subfascial subcostal tunnel. As the severely dilated right ventricle compressed the apex of the left ventricle, which was also dilated to the mid-back zone of the left hemithorax, the whole length of the Extracorporeal BIVAD apical cannula had to remain within the thorax; however, the cannula was removed from the body by creating a tunnel at the 7th intercostal space. In the long-term follow-up, this compulsory modification has proven to be safe and effective.

The effects of chronic usage of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on contrast-induced nephropathy in low-risk patients [corrected].

OBJECTIVE: There is conflicting data about the role of renin- angiotensin- aldosterone system (RAAS) blockers in contrast-induced nephropathy (CIN) pathophysiology. In this study, we aimed to investigate the effects of chronic usage of RAAS blocker drugs on development of CIN in low risk patients. METHODS: Study was designed as a prospective cohort study. A total of 295 patients were enrolled in the study. Study population was consisted of three subgroups according to prior usage of RAAS blockers: no RAAS blocker group (n=95), angiotensin-converting enzyme inhibitor (ACEI) group (n=106), angiotensin receptor blocker (ARB) group (n=94). CIN was defined as an increase of ≥25% in creatinine over the baseline value or 0.5 mg/dL rise within 48-72 h of angiography. Mehran score was calculated for each patient. Baseline variables and percentage of CIN were compared with ANOVA, Mann-Whitney U, Kruskal-Wallis and Pearson Chi-square tests between groups. In order to determine the independent predictors of CIN, binary logistic regression analyses were performed. RESULTS: CIN occurred in 18 patients (17.0%) in the ACEI group, 17 patients (18.1%) in ARB group and 7 patients (7.4%) in the no RAAS group. CIN occurrence was significantly higher in RAAS than no RAAS group (17.5% vs. 7.4%, p=0.01). Chronic RAAS blocker administration was an independent predictor of CIN (OR=2.69; 95% CI: 1.025-7.067; p=0.04). Mehran score was the only other independent predictor for CIN (OR=1.15; 95% CI: 1.019-1.310; p=0.02). CONCLUSION: In patients with near normal renal functions who are undergoing elective coronary procedure, chronic usage of ACEI and ARB increases the risk of CIN.

[Coronary invasive procedures in women]. / Kadinlarda koroner invaziv girisimler.

Cardiovascular diseases are the most common etiology in women deaths worldwide. Despite this fact, coronary artery disease is usually known as a disease of men, and its importance in women health is not emphasized so much. In many registries, it has been shown that, female patients are opposed to less coronary invasive procedures than men. The reasons of this conservative strategy in women are, the older age, the more advanced coronary atherosclerosis at the time of diagnosis and smaller coronary arteries. Because of these factors, female patients are also prone to more complication rates than men. Until a few years ago, there had been little knowledge about gender related differences in diagnosis and management of coronary artery disease. In many of the large angiographic trials, most of the female patients were excluded from the studies, because of age and small coronary vessels. But now, with growing awareness of gender related differences in management of coronary artery disease, more female patients are included in trials, and more post-hoc analysis about gender factor are made.