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 relation of right ventricular outflow tract measurements with in-hospital clinical outcomes after tricuspid valve surgery.

Right ventricular (RV) function is a determining factor for clinical outcomes in patients undergoing tricuspid valve surgery (TVS). Our aim was to investigate the importance of the function of the right ventricular outflow tract (RVOT), which is an important anatomical region of the RV, in patients underwent TVS. 104 patients who underwent TVS were analyzed retrospectively. Patients with previous cardiac surgery, congenital heart disease, or heart failure were excluded. The parasternal short-axis view at the level of the aortic root was used to measure RVOT dimensions and RVOT fractional shortening (RVOT-FS). The effect of RVOT diameter and function on major adverse cardiac events (MACE) after TVS was investigated. In our study, MACE, consisting of pacemaker implantation, acute kidney injury, postoperative atrial fibrillation and mortality, was developed at 44 (42.3%) patients.We compared the predictive performances of RVOT end-systolic (RVOTs) diameter, RVOT end-diastolic (RVOTd) diameter, RVOT-FS and RV diameters in prediction of MACE. The model including the RVOTs had higher AUC, R2 and likelihood ratio X2 values (0.775, 0.287 and 25.0, respectively) than RVOTd (0.770, 0.279 and 24.2, respectively) and RVOT-FS (0.750, 0.215 and 18.1, respectively). RVOT diameters showed better performance in predicting MACE than RV diameters. Moreover, there was statistically significant association between RVOTs, RVOTd and MACE (p value were 0.014 and 0.027, respectively), while no association between RVOT-FS and MACE (p value was 0.177). In summary, we determined that the RVOT diameters are important predictors for the in-hospital clinical outcomes of patients who underwent TVS.

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.

Persistent right heart dilatation after percutaneous mitral balloon valvuloplasty: A weird coexistence of iatrogenic and congenital shunts.

We present an interesting case of concomitant congenital anomalies with an iatrogenic defect. The female patient underwent a percutaneous mitral balloon valvuloplasty due to rheumatic mitral stenosis. Unfortunately, an iatrogenic atrial septal defect (ASD) transpired during the procedure. Upon post-procedure examination, partial anomalous pulmonary venous (PAPVR) return was observed. The patient was symptomatic; on imaging, dilatation of the right heart chambers were detected. In addition, another crucial point was that the patient was planning a pregnancy, thus robotic surgery for iatrogenic ASD and PAPVR return was recommended. After a successful operation, the patient was asymptomatic and the size of right heart chambers were normalized.

A novel approach of tricuspid valve repair: mitralization of tricuspid valve.

OBJECTIVES: This study presents the mid-term results of a novel tricuspid valve (TV) repair strategy defined as 'mitralization of TV' (resection and plication of the posterior leaflet, ring implantation, optional leaflet procedures) applied for the correction of tricuspid regurgitation (TR). METHODS: Between 2017 and 2020, a total of 22 patients underwent concomitant TV repair using mitralization of the TV. Fourteen of the patients had functional TR (2 of them had severe tethering), 5 patients had prolapse and 3 patients had rheumatic involvement. RESULTS: There was no in-hospital mortality. Moderate or severe TR was not observed in any patient in echocardiographic evaluations before discharge. The mean follow-up duration was 30.9 + 6.2 months. Moderate-to-severe TR-free survival was 100% in the second year and 94.7% in the third year. CONCLUSIONS: Mitralization of the TV is a safe and effective treatment modality in terms of its mid-term results. This new technique provides an innovative perspective for the treatment of TR, especially in complex TV pathologies.

Cost-Effectiveness Analysis of the Triclip™ Transcatheter Tricuspid Valve Repair System in Patients with Tricuspid Regurgitation.

BACKGROUND: Tricuspid regurgitation is a condition that affects 1.6 million patients in the United States and is independently associated with morbidity and mortality. The TriClip™ procedure repairs the tricuspid valve without the need for open-heart surgery. The aim of this study is to evaluate the cost-effectiveness of TriClip™ treatment in patients with advanced tricuspid regurgitation from the Turkish reimbursement agency perspective. METHODS: Within the scope of this study, the general literature was searched in order to reach data on tricuspid regurgitation. The utilization of health care services used in the expert panel was re-calculated with the current reimbursement costs to determine the cost of heart failure in Turkey. In this study, Markov analysis, Tornado analysis, cost-effectiveness analysis, and partitioned survival analysis have been performed to determine whether TriClip™ is an effective treatment method compared to medication treatment. RESULTS: In according to calculations, 5-year survival rate was found as 49.91% for medication treatment and 57.64% for TriClip™ treatment. According to the analysis performed, the cost of medication treatment was calculated as €3879.72 and TriClip™ Transcatheter Tricuspid Valve Repair System treatment as €25 661.15 for a 60-month period in patients with tricuspid regurgitation and New York Heart Association III-IV. In the calculation, it was found that TriClip™ treatment gave patients an average of 1.64 life years and it was found to be cost-effective compared to medication treatment. CONCLUSIONS: Considering the positive effect of TriClip™ treatment on patients with tricuspid regurgitation in terms of mortality and regression of the heart failure stage, as recommended in the guidelines, widespread of its use has great importance.

[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.

Multimodality imaging of an aortic graft infection.

Aortic prosthetic vascular graft infections (PVGI) are rare complications of the aortic surgery, with an incidence of 0.5%-6%. Although rare, they carry mortality rates as high as 25%-88%. Improvement in diagnostic imaging modalities in the last two decades, together with early diagnosis, aortic PVGI associated mortality was reduced. These imaging methods include transesophageal echocardiography (TEE), computed tomography angiography (CTA), and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). In this case report, we focus mainly on three imaging modalities as TEE, CTA, and 18F-FDG PET/CT and showed their role in the assessment of aortic PVGI.

Red Cell Distribution Width with CHADS2 and CHA2DS2-VASc score is associated with Post-operative Atrial Fibrillation after Coronary Artery Bypass Grafting.

BACKGROUND: The use of the CHA2DS2-VASc scoring system and red cell distribution width (RDW) as post-op Atrial Fibrillation (POAF) predictors may be promising for the identification of patients that are at a higher risk of POAF. METHODS: A total of 358 patients (57 patients with POAF, and 301 patients with non-POAF ) with sinus rhythm undergoing a coronary artery bypass graft (CABG) operation were included in the study retrospectively. Preoperative RDW levels and electrocardiograms with sinus rhythm were recorded. Patients with at least one 12-lead electrocardiogram with atrial fibrillation in the postoperative period, with or without medical or electrical cardioversion, were considered to have postoperative atrial fibrillation. A CHADS2 and CHA2DS2-VASc score was calculated for all of the patients. RESULTS: RDW levels were significantly higher in POAF group. RDW levels were significantly correlated with CHADS2 ( r = 0.15, P = .007) and CHA2DS2-VASc (r = 0.19 P = .0001) scores. CHA2DS2-VASc scores were significantly higher in patients with POAF, whereas CHADS2 scores did not differ between groups. In multivariate analysis, left atrial diameter (LAD) (OR:2.44 [95% CI 1.16 - 5.1], P = .018), age (OR:1.04 [95% CI 1.01 - 1.08], P = .01), and RDW (OR:1.16 [95% CI 1.0 - 1.36], P = .05) were found to be predictive for POAF. The area under the receiver-operating characteristic curve of RDW was 0.65 (0.57 - 0.72, P = .0001) with 68.4% sensitivity and 51.2 % specificity to predict POAF. CONCLUSION: Our study showed that age, LAD, and the reduced probability of RDW are predictors of POAF, and that RDW is strongly associated with the thromboembolic risk as determined by CHADS2 and CHA2DS2-VASc scores.

Acute myocardial infarction complicated with ventricular septal rupture and intracranial hemorrhage.

Ventricular septal rupture (VSR) is a rare but fatal complication of acute myocardial infarction (AMI) with an associated mortality that ranges from 41% to 80%. The treatment consists of supplemental oxygenation, afterload reduction, intraaortic balloon pump, and surgical repair. In selected patients, extracorporeal membrane oxygenation (ECMO) and/or percutaneous closure of the defect can be considered if anatomically appropriate. Echocardiography evaluates the morphology and location of the defect, anatomical concerns for percutaneous closure, and accompanying pathologies. We present a 48-year-old man with inferior myocardial infarction and basal VSR who was not a candidate for percutaneous closure. Surgery was planned, but he died from extensive subarachnoid and intracranial hemorrhage.

Is right atrioventricular valve always tricuspid?

A 71-year-old male with a medical history of hypertension was admitted to emergency department with hypertensive pulmonary edema. The patient appeared anxious and diaphoretic, and physical examination revealed tachypnea, crepitant rales in the both lungs and a systolic ejection murmur at the right sternal border, radiating to the both carotid arteries. The electrocardiography showed sinus tachycardia with indications of left ventricle hypertrophy Before the aortic valve surgery, transesophageal echocardiography (TEE) was performed for detailed evaluation of the aortic valve. Two-dimensional TEE showed mild tricuspid valve regurgitation and only two of three leaflets of the tricuspid valve at a time.

Papillary Muscle Free Strain in Patients with Severe Degenerative and Functional Mitral Regurgitation / Free Strains de Músculos Papilares em Pacientes com Insuficiência Mitral Funcional e Degenerativa Grave

Abstract Fundamento: The role of papillary muscle function in severe mitral regurgitation with preserved and reduced left ventricular ejection fraction and the method of choice to evaluate PM have still been the subjects of controversy. Objectives: To evaluate and compare papillary muscle function in and between patients with severe degenerative and functional mitral regurgitation by using the free strain method. Methods: 64 patients with severe mitral regurgitation - 39 patients with degenerative mitral regurgitation (DMR group) and 25 patients with severe functional mitral regurgitation (FMR group) - and 30 control subjects (control group) were included in the study. Papillary muscle function was evaluated through the free strain method from apical four chamber images of the anterolateral papillary muscle (APM) and from apical three chamber images of the posteromedial papillary muscle (PPM). Global left ventricular longitudinal and circumferential strains were evaluated by applying 2D speckle tracking imaging. Results: Global left ventricular longitudinal strain (DMR group, -17 [-14.2/-20]; FMR group, -9 [-7/-10.7]; control group, -20 [-18/-21] p < 0.001), global left ventricular circumferential strain (DMR group, -20 [-14.5/-22.7]; FMR group, -10 [-7/-12]; control group, -23 [-21/-27.5] p < 0.001) and papillary musle strains (PPMS; DMR group, -30.5 [-24/-46.7]; FMR group, -18 [-12/-30]; control group; -43 [-34.5/-39.5] p < 0.001; APMS; DMR group, (-35 [-23.5/-43]; FMR group, -20 [-13.5/-26]; control group, -40 [-32.5/-48] p < 0.001) were significantly different among all groups. APMS and PPMS were highly correlated with LVEF (p < 0.001, p < 0.001; respectively), GLS (p < 0.001, p < 0.001; respectively) and GCS (p < 0.001, p < 0.00; respectively) of LV among all groups. No correlation was found between papillary muscle strains and effective orifice area (EOA) in both groups of severe mitral regurgitation. Conclusions: Measuring papillary muscle longitudinal strain by the free strain method is practical and applicable. Papillary muscle dysfunction plays a small role in severe MR due to degenerative or functional causes and papillary muscle functions in general seems to follow left ventricular function. PPM is the most affected PM in severe mitral regurgitation in both groups of DMR and FMR.

Resumo Fundamento: O papel da função do músculo papilar na regurgitação mitral grave com fração de ejeção do ventrículo esquerdo preservada e reduzida e o método de escolha para avaliar PM ainda são objetos de controvérsia. Objetivos: Avaliar e comparar a função dos músculos papilares entre pacientes com insuficiência mitral funcional e degenerativa pelo método free strain. Métodos: 64 pacientes com insuficiência mitral grave - 39 pacientes com insuficiência mitral degenerativa grave (grupo IMD) e 25 com insuficiência mitral funcional grave (grupo IMF) - e 30 indivíduos controle (grupo controle) foram incluídos no estudo. A função dos músculos papilares foi avaliada pelo método free strain a partir de imagens apicais quatro-câmaras do músculo papilar anterolateral (MPA) e imagens apicais três-câmaras do músculo papilar posteromedial (MPP). Strains circunferenciais e longitudinais globais do ventrículo esquerdo foram avaliados por meio de imagens bidimensionais a partir do rastreamento de conjunto de pontos de cinza (speckle tracking). Resultados: O strain longitudinal global do ventrículo esquerdo (grupo IMD, -17 [-14,2/-20]; grupo IMF, -9 [-7/-10,7]; grupo controle, -20 [-18/-21] p < 0,001); strain circunferencial global do ventrículo esquerdo (grupo IMD, -20 [-14,5/-22,7]; grupo IMF, -10 [-7/-12]; grupo controle, -23 [-21/-27,5] p < 0,001) e strains de músculos papilares (MPP; grupo IMD, -30,5 [-24/-46,7]; grupo IMF, -18 [-12/-30]; grupo controle; -43 [-34,5/-39,5] p < 0,001; MPA; grupo IMD, (-35 [-23,5/-43]; grupo IMF, -20 [-13,5/-26]; grupo controle, -40 [-32,5/-48] p < 0,001) mostraram-se significativamente diferentes nos grupos. MPA e MPP mostraram-se altamente correlacionados com a FEVE (p < 0,001, p < 0,00; respectivamente), SLG (p < 0,001, p < 0,001; respectivamente) e SCG (p < 0,001, p < 0,001; respectivamente) do VE entre todos os grupos. Não foi encontrada correlação entre os strains de músculos papilares e área eficaz do orifício (AEO) nos grupos de insuficiência mitral grave. Conclusões: A medição do strain longitudinal de músculos papilares pelo método free strain é prática e aplicável. A disfunção dos músculos papilares tem um papel pequeno em IM grave devido a causas degenerativas e funcionais, e a função dos músculos papilares, em general, parece seguir a função ventricular esquerda. O MPP é o MP mais afetado na insuficiência mitral em ambos os grupos, IMD e IMF.

Left atrial remodeling in patients undergoing percutaneous mitral valve repair with the MitraClip system: an advanced echocardiography study.

BACKGROUND: The goal of this study was to determine changes in left atrial (LA) function with two-dimensional speckle tracking echocardiography (2DSTE) and real-time full-volume three-dimensional echocardiography (RT3DE) after percutaneous mitral valve repair with the MitraClip system. Furthermore, we investigated whether baseline and/or changes in LA function after MitraClip repair had any impact on prognosis. METHODS: A total of 25 consecutive patients (age: 57±12 years, 76% male) with moderate-to-severe or severe mitral regurgitation (MR) were included. Patients underwent 2DSTE and RT3DE before the clip implantation and after the 12-month follow-up. Prognostic data were also recorded via the use of telephone calls and follow-up visits for 12 months after the procedure. RESULTS: Compared with the baseline, the LA reservoir strain (LA-Res) (7.66±4.3% vs 11.15±7.5%, P<.001) and LA contraction strain (LA-Pump) (4.64±4.3% vs 7.63±5.8%, P=.001) improved significantly after MitraClip repair; significant improvements were also seen in three-dimensional (3D) minimum LA volume index (LAV min) and maximum LA volume index (LAV max). On the other hand, conventional LA indices did not change. In total, eleven major adverse cardiac events (MACE) were observed at the 1-year follow-up. In univariate analyses, the preprocedural echocardiographic parameters that were associated with the MACE within 1 year after MitraClip repair were 3D-LAV min and LA-Res. Furthermore, these indices significantly correlated with improved functional parameters and MR reduction. CONCLUSION: In conclusion, a successful MitraClip procedure can reverse the process of LA remodeling within 12 months, and this can be detected by 2DSTE and RT3DE. Also, patients with preprocedural lower LA-Res and higher 3D-LAV min had the worst prognoses at the 1-year follow-up.

Association between non-coding polymorphisms of HOPX gene and syncope in hypertrophic cardiomyopathy.

OBJECTIVE: Homeodomain Only Protein X (HOPX) is an unusual homeodomain protein which regulates Serum Response Factor (SRF) dependent gene expression. Due to the regulatory role of HOPX on SRF activity and the regulatory role of SRF on cardiac hypertrophy, we aimed to investigate the relationship between HOPX gene variations and hypertrophic cardiomyopathy (HCM). METHODS: In this study, designed as a case-control study, we analyzed coding and flanking non-coding regions of the HOPX gene through 67 patients with HCM and 31 healty subjects. Certain regions of the gene were investigated by Single Stranded Conformation Polymorphism (SSCP) and Restriction Fragment Length Polymorphism (RFLP). Statistical analyses of genotypes and their relationship with clinical parameters were performed by chi-square, Kruskal-Wallis and the Fisher's exact test. RESULTS: In 5' Untranslated Region (UTR) and intronic region of the HOPX gene, we found a C>T substitution and an 8-bp insertion/deletion (In/Del) polymorphism, respectively. These two polymorphisms seemed to constitute an haplotype. While the frequency of homozygous genotypes of In/Del and C/T polymorphisms were found significantly lower in the patients with syncope (p=0.014 and p=0.017, respectively), frequency of their heterozygous genotypes were found significantly higher in the patients with syncope (p=0.048 and p=0.030, respectively). CONCLUSION: Though there was not found any mutation in coding sequence of HOPX gene, two non-coding polymorphisms were found related to syncope in HCM patients. While homozygous status of these polymorphisms was found to be protective against the syncope, their heterozygous status seemed to be a risk factor for syncope in HCM patients. Our results suggest that HOPX may contribute to pathogenesis or manifestation of HCM as a modifier gene.

Acute ST-elevation myocardial infarction in early puerperium due to severe left main coronary stenosis in a woman with familial hyperlipidaemia.

Acute myocardial infarction (AMI) is a rare but often catastrophic event during pregnancy, delivery or puerperium, leading to a high mortality rate. It has different pathogenic mechanisms, such as atherosclerosis, vasospasm, thrombosis and coronary dissection. Although MI has been reported in pregnant women at all stages of pregnancy and postpartum, it occurs more commonly in the third trimester and most commonly involves the anterior wall. Evidence suggests that pregnancy itself is an independent risk factor for MI, conferring a three- to four-fold higher risk than that of nonpregnant women matched for age, possibly due to the unique physiological changes required to meet the demands of a growing foetus. We report a case of a 27-year-old woman with familial hyperlipidaemia presenting with myocardial infarction six days after caesarean delivery, secondary to severe left main coronary stenosis (LMCA), who was treated with emergency coronary artery bypass grafting (CABG).

Thrombolytic therapy for the treatment of prosthetic heart valve thrombosis in pregnancy with low-dose, slow infusion of tissue-type plasminogen activator.

BACKGROUND: Prosthetic valve thrombosis during pregnancy is life-threatening for mother and fetus, and the treatment of this complication is unclear. Cardiac surgery in pregnancy is associated with very high maternal and fetal mortality and morbidity. Thrombolytic therapy has rarely been used in these patients. The aim of this study is to evaluate the safety and efficacy of low-dose (25 mg), slow infusion (6 hours) of tissue-type plasminogen activator for the treatment of prosthetic valve thrombosis in pregnant women. METHODS AND RESULTS: Between 2004 and 2012, tissue-type plasminogen activator was administered to 24 consecutive women in 25 pregnancies with 28 prosthetic valve thrombosis episodes (obstructive, n=15; nonobstructive, n=13). Mean age of the patients was 29±6 years. Thrombolytic therapy sessions were performed under transesophageal echocardiography guidance. The mean dose of tissue-type plasminogen activator used was 48.7±29.5 mg (range, 25-100 mg). All episodes resulted in complete thrombus lysis after thrombolytic therapy. One patient had placental hemorrhage with preterm live birth at the 30th week, and 1 patient had minor bleeding. CONCLUSIONS: Low-dose, slow infusion of tissue-type plasminogen activator with repeated doses as needed is an effective therapy with an excellent thrombolytic success rate for the treatment of prosthetic valve thrombosis in pregnant women. This protocol also seems to be safer than cardiac surgery or any alternative medical strategies published to date. Thrombolytic therapy should be considered first-line therapy in pregnant patients with prosthetic valve thrombosis.