Sex Differences in Transthyretin Cardiac Amyloidosis: Unraveling the Complexities in Epidemiology, Pathophysiology, Diagnosis, and Treatment.

Transthyretin cardiac amyloidosis (ATTR-CA) is characterised by the deposition of transthyretin amyloid fibrils in the heart. ATTR-CA affects both men and women although there is evidence of sex differences in prevalence and clinical presentation. PURPOSE OF REVIEW: This review paper aims to comprehensively examine and synthesise the existing literature on sex differences in ATTR-CA. RECENT FINDINGS: The prevalence of ATTR-CA is higher in males although the male predominance is more apparent in older patients in the wild type form and in TTR genetic variants that predominantly result in a cardiac phenotype in the hereditary variant. Women tend to have less left ventricular hypertrophy (LVH) and a higher ejection fraction at clinical presentation which may contribute to a later diagnosis although the prognosis appears to be similar in both sexes. Female sex is a predictor of a good response to tafamidis 20 mg in TTR polyneuropathy but otherwise there are no data on sex differences in the efficacy of other treatments for ATTR-CA. It is crucial to define specific sex differences in ATTR-CA. A lower cut-off value for LVH in women may be needed to improve diagnosis. It is necessary to increase female representation in clinical trials to better understand possible sex differences in therapeutic management.

Invasive management of significant tricuspid regurgitation in clinical practice.

BACKGROUND: Tricuspid regurgitation (TR) is a prevalent condition inside valvular heart disease (VHD) with relevant prognosis implications. However, concordance between real management in clinical practice and invasive treatment recommendations of European Society of Cardiology (ESC) guidelines is unknown. METHODS: A substudy of ESC VHD II survey was performed to evaluate the real treatment of TR compared to the clinical ESC guidelines recommendations published in 2012, 2017 and 2021 was performed. TR cases with surgical indication were divided in 3 groups: 1: severe isolated TR without previous left VHD; 2: moderate/severe TR and concomitant severe left VHD; 3: severe TR plus previous left VHD surgery. RESULTS: Of 902 patients assessed, 123 had significant TR. Fifty (41%) cases demonstrated ESC guidelines 2012-2017 Class I or IIa recommendations for invasive treatment: 9(18%) of group 1, 37(74%) of group 2 and 4(8%) of group 3. Surgery was performed in 24 patients (48%); 1 in group 1(4%), 22 in group 2(92%) and 1 in group 3(4%). Overall concordance was 48% (group 1: 11%; group 2: 59%; group 3: 25%). Regarding the 2021 ESC guidelines only one patient changed groups with an overall concordance of 47% (group 1: 10%; group 2: 59%; group 3: 25%). CONCLUSION: Concordance between 2012, 2017 and 2021 ESC guidelines recommendations and clinical practice for TR surgical intervention is low, especially in those without concomitant severe left VHD. These results suggest the need to improve further guideline implementation and alternative treatments, such as percutaneous, which could resolve potential discrepancies in those clinical scenarios.

Association of Genetic Variants With Outcomes in Patients With Nonischemic Dilated Cardiomyopathy.

BACKGROUND: The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. OBJECTIVES: The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. METHODS: Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR). RESULTS: After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.09-2.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction ≤35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene. CONCLUSIONS: In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene.

Founder mutation in myosin-binding protein C with an early onset and a high penetrance in males.

OBJECTIVE: One of the challenges in hypertrophic cardiomyopathy (HCM) is to determine the pathogenicity of genetic variants and to establish genotype/phenotype correlations. This study aimed to: (1) demonstrate that MYBPC3 c.2149-1G>A is a founder pathogenic variant, (2) describe the phenotype and clinical characteristics of mutation carriers and (3) compare these patients with those with the most frequent pathogenic HCM variants: MYBPC3 p.Arg502Trp/Gln. METHODS: We reviewed genetic tests performed in HCM probands at our institution. We carried out transcript analyses to demonstrate the splicing effect, and haplotype analyses to support the founder effect of MYBPC3 c.2149-1G>A. Carriers with this mutation were compared with those from MYBPC3 p.Arg502Trp/Gln in terms of presentation features, imaging and outcomes. RESULTS: MYBPC3 c.2149-1G>A was identified in 8 of 570 probands and 25 relatives. Penetrance was age and sex dependent, 50.0% of the carriers over age 36 years and 75.0% of the carriers over 40 years showing HCM. Penetrance was significantly higher in males: in carriers older than 30 years old, 100.0% of males vs 50.0% of females had a HCM phenotype (p=0.01). Males were also younger at diagnosis (32±13 vs 53±10 years old, p<0.001). MYBPC3 c.2149-1G>A resulted in an abnormal transcript that led to haploinsufficiency and was segregated in two haplotypes. However, both came from one founder haplotype. Affected carriers showed a better functional class and higher left ventricular ejection fraction (LVEF) than patients with MYBPC3 p.Arg502Trp/Gln (p<0.05 for both). Nevertheless, the rate of major adverse outcomes was similar between the two groups. CONCLUSIONS: MYBPC3 c.2149-1G>A splicing variant is a founder mutation. Affected males show an early onset of HCM and with higher penetrance than women. Carriers show better functional class and higher LVEF than MYBPC3 p.Arg502Trp/Gln carriers, but a similar rate of major adverse outcomes.

Predictors of outcome in a Spanish cohort of patients with Fabry disease on enzyme replacement therapy.

Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in patients on ERT. STUDY DESIGN: Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). RESULTS: In 69 patients (42 males, 27 females, mean age 44.6±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242-128mg/g (p=0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR≤60ml/min/1.73m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043) and in males and in females. Lower baseline eGFR was associated with a 3- to 7-fold increase the risk of clinical events in different Cox models. CONCLUSIONS: GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes.

Mid-Term Results of Surgical Treatment of Atrial Fibrillation in Valvular Heart Disease Assesed by Speckle Tracking Echocardiography / Resultados em Médio Prazo do Tratamento da Fibrilação Atrial na Doença Valvular Cardíaca Avaliados por Ecocardiografia com Speckle Tracking

Abstract Background: Atrial fibrillation frequently affects patients with valvular heart disease. Ablation of atrial fibrillation during valvular surgery is an alternative for restoring sinus rhythm. Objectives: This study aimed to evaluate mid-term results of successful atrial fibrillation surgical ablation during valvular heart disease surgery, to explore left atrium post-ablation mechanics and to identify predictors of recurrence. Methods: Fifty-three consecutive candidates were included. Eligibility criteria for ablation included persistent atrial fibrillation <10 years and left atrium diameter < 6.0 cm. Three months after surgery, echocardiogram, 24-hour Holter monitoring and electrocardiograms were performed in all candidates who maintained sinus rhythm (44 patients). Echo-study included left atrial deformation parameters (strain and strain rate), using 2-dimensional speckle-tracking echocardiography. Simultaneously, 30 healthy individuals (controls) were analyzed with the same protocol for left atrial performance. Significance was considered with a P value of < 0.05. Results: After a mean follow up of 17 ± 2 months, 13 new post-operative cases of recurrent atrial fibrillation were identified. A total of 1,245 left atrial segments were analysed. Left atrium was severely dilated in the post-surgery group and, mechanical properties of left atrium did not recover after surgery when compared with normal values. Left atrial volume (≥ 64 mL/m2) was the only independent predictor of atrial fibrillation recurrence (p = 0.03). Conclusions: Left atrial volume was larger in patients with atrial fibrillation recurrence and emerges as the main predictor of recurrences, thereby improving the selection of candidates for this therapy; however, no differences were found regarding myocardial deformation parameters. Despite electrical maintenance of sinus rhythm, left atrium mechanics did not recover after atrial fibrillation ablation performed during valvular heart disease surgery.

Resumo Fundamento: A fibrilação atrial frequentemente afeta pacientes com doenças das valvas cardíacas. A ablação da fibrilação atrial durante a cirurgia das válvulas é uma alternativa para restaurar o ritmo sinusal. Objetivos: Este estudo teve como objetivos avaliar resultados em médio prazo da ablação cirúrgica bem sucedida da FA durante cirurgia para doença valvar, para explorar a mecânica do AE após a ablação e identificar preditores de recorrência. Métodos: Foram incluídos 53 candidatos consecutivos. Os critérios de elegibilidade para ablação foram fibrilação atrial persistente <10 anos e diâmetro do átrio esquerdo < 6 cm. Três meses após a cirurgia, foram realizados ecocardiografia, Holter por 24 horas, e eletrocardiografias em todos os candidatos que mantiveram o ritmo sinusal (44 pacientes). O estudo eco incluiu parâmetros de deformação ao átrio esquerdo (strain e taxa de strain) usando ecocardiografia bidimensional com speckle tracking. Simultaneamente, 30 indivíduos sadios (controles) foram analisados com o mesmo protocolo para o desempenho do átrio esquerdo. Um valor de P < 0,05 foi considerado significativo. Resultados: Após um período médio de acompanhamento de 17 ± 2 meses, 13 novos casos de fibrilação atrial no pós-operatório foram identificados. Um total de 1245 segmentos do átrio esquerdo foi analisado. O grupo pós-cirúrgico apresentou dilatação grave do átrio esquerdo, e as propriedades mecânicas do átrio esquerdo não se recuperaram após a cirurgia quando comparadas com valores normais. O volume do átrio esquerdo (≥ 64 mL/m2) foi o único preditor independente de recorrência de fibrilação atrial (p = 0,03). Conclusões: O volume do átrio esquerdo foi maior nos pacientes com fibrilação atrial recorrente, e desponta como o principal preditor de recorrência, melhorando, assim, a seleção de candidatos para essa terapia. No entanto, não foram encontradas diferenças em relação aos parâmetros de deformação do miocárdio. Apesar da manutenção elétrica do ritmo sinusal, a função mecânica do átrio esquerdo não se recuperou após a ablação da fibrilação atrial realizada durante a cirurgia para doença da valva cardíaca.

Mid-Term Results of Surgical Treatment of Atrial Fibrillation in Valvular Heart Disease Assesed by Speckle Tracking Echocardiography.

BACKGROUND: Atrial fibrillation frequently affects patients with valvular heart disease. Ablation of atrial fibrillation during valvular surgery is an alternative for restoring sinus rhythm. OBJECTIVES: This study aimed to evaluate mid-term results of successful atrial fibrillation surgical ablation during valvular heart disease surgery, to explore left atrium post-ablation mechanics and to identify predictors of recurrence. METHODS: Fifty-three consecutive candidates were included. Eligibility criteria for ablation included persistent atrial fibrillation <10 years and left atrium diameter < 6.0 cm. Three months after surgery, echocardiogram, 24-hour Holter monitoring and electrocardiograms were performed in all candidates who maintained sinus rhythm (44 patients). Echo-study included left atrial deformation parameters (strain and strain rate), using 2-dimensional speckle-tracking echocardiography. Simultaneously, 30 healthy individuals (controls) were analyzed with the same protocol for left atrial performance. Significance was considered with a P value of < 0.05. RESULTS: After a mean follow up of 17 ± 2 months, 13 new post-operative cases of recurrent atrial fibrillation were identified. A total of 1,245 left atrial segments were analysed. Left atrium was severely dilated in the post-surgery group and, mechanical properties of left atrium did not recover after surgery when compared with normal values. Left atrial volume (≥ 64 mL/m2) was the only independent predictor of atrial fibrillation recurrence (p = 0.03). CONCLUSIONS: Left atrial volume was larger in patients with atrial fibrillation recurrence and emerges as the main predictor of recurrences, thereby improving the selection of candidates for this therapy; however, no differences were found regarding myocardial deformation parameters. Despite electrical maintenance of sinus rhythm, left atrium mechanics did not recover after atrial fibrillation ablation performed during valvular heart disease surgery.

Functional anatomy of aortic regurgitation. Role of transesophageal echocardiography in aortic valve-sparing surgery.

INTRODUCTION AND OBJECTIVES: The aim was to evaluate the usefulness of transesophageal echocardiography (TEE) for the preoperative functional anatomical assessment of patients with aortic regurgitation (AR) to identify those eligible for valve-sparing surgery (VSS). METHODS: We determined the accuracy and diagnostic value of TEE for identifying underlying lesions and mechanisms in 66 patients who underwent surgery for severe AR by comparing TEE findings with those obtained on surgical inspection. The usefulness of TEE for predicting the feasibility of VSS was determined. RESULTS: The overall diagnostic accuracy of TEE was excellent (87%, kappa=0.82), with valve prolapse being the principle cause of discrepancy between the methods (in 23/27 cases; 85%). Three anatomical forms of dilatation of the ascending aorta (AA) were correctly classified (accuracy >88%; kappa 0.83): supratubal aneurysm (19 patients), aortic root aneurysm (4), and annuloaortic ectasia (24). The mechanism underlying AR was identified with an accuracy of 85% (kappa 0.8) and there was a significant association between the type of mechanism identified by TEE and the success of VSS (P< .001): VSS was successful in 73% of patients with dilatation of a functional annulus (i.e. with tethering), but aortic valve replacement was required in 78% with prolapses, 90% with thickened leaflets with restricted movement, and 100% with perforation. There was also a relationship between the type of aneurysm and the technique required for AA replacement (P=.004). CONCLUSIONS: Use of TEE enabled the mechanism underlying AR to be accurately identified. There was a high level of agreement with surgical inspection and the technique was useful for predicting the feasibility of VSS and the surgical procedure for AA replacement.

The reno-protective effect of hydration with sodium bicarbonate plus N-acetylcysteine in patients undergoing emergency percutaneous coronary intervention: the RENO Study.

OBJECTIVES: This study was designed to determine the effectiveness of a protocol for rapid intravenous hydration to prevent contrast-induced nephropathy (CIN) in patients undergoing emergency percutaneous coronary intervention (PCI). BACKGROUND: Contrast-induced nephropathy frequently complicates PCI, resulting in prolonged hospitalization and increased in-hospital and long-term morbidity and mortality. Little is known regarding prevention of CIN in patients undergoing urgent PCI. METHODS: We conducted a prospective, controlled, randomized, single-center trial in 111 consecutive patients with acute coronary syndrome undergoing emergency PCI. As part of the hydration therapy, 56 patients (group A) received an infusion of sodium bicarbonate plus N-acetylcysteine (N-AC) started just before contrast injection and continued for 12 h after PCI. The remaining 55 patients (group B) received the standard hydration protocol consisting of intravenous isotonic saline for 12 h after PCI. In both groups, 2 doses of oral N-AC were administered the next day. RESULTS: The 2 groups were similar with respect to age, gender, diabetes mellitus, and baseline serum creatinine. A serum creatinine concentration >0.5 mg/dl from baseline after emergency PCI was observed in 1 patient in group A (1.8%) and in 12 patients in group B (21.8%; p < 0.001). Acute anuric renal failure was observed in 1 patient (1.8%) in group A and in 7 patients (12.7%) in group B (p = 0.032). CONCLUSIONS: Rapid intravenous hydration with sodium bicarbonate plus N-AC before contrast injection is effective and safe in the prevention of CIN in patients undergoing emergency PCI.

Terbinafina oral en tiña pedis: estudio clínico multicéntrico / Oral terbinafine in tinea pedis: multicentric clinical study

Se presenta la experiencia clínica multicéntrica Uruguay-Chile en el tratamiento de la tiña pedis con terbinafina oral administrada por 2 semanas, con períodos de observación postratamiento a las 4 y 8 semanas de inicio del estudio. Se incluyen 67 pacientes,39 mujeres y 28 hombres, con una edad promedio de 38,9 años, que presentaban el cuadro clínico de tiña pedis (forma interdigital y formas plantares difusas, ya sea uni o bilaterales), el que fue confirmado por la presencia de dermatofitos en el cultivo micológico inicial (79,1 por ciento de los casos trichophyton rubrum). Se evaluaron signos clínicos variados: eritema, descamación, vesiculización, presencia de pústulas, exudación, costras y síntoma prurito. La evaluación micológica se efectuó mediante examen directo y cultivo. Los signos y síntomas clínicos mejoraron durante todo el seguimiento, alcanzando entre 61,2 por ciento al 100 por ciento de mejoría total de estos parámetros a las 8 semanas de seguimiento. Los exámenes micológicos se fueron negativizando progresivamente, alcanzando en la evaluación final a las 8 semanas un 92 por ciento de exámenes directos y un 85 por ciento de cultivos negativos, respectivamente. Recaídas con cultivos micológicos positivos fueron observadas en 2 casos (4,3 por ciento). El medicamento fue, en general, bien tolerado, y los efectos adversos más frecuentes fueron gastrointestinales, presentes en 7 pacientes. No se registraron alteraciones de parámetros bioquímicos de significación. En conclusión, la terbinafina (LAMISIL) se presenta como una nueva medicación antimicótica sistémica de alta eficacia en cortos períodos de tratamiento en variadas formas de tiña pedis