Therapeutics – ABC CARDIOL

IJCS

Editorial

Cardiac Myosin Inhibitors in Patients with Hypertrophic Cardiomyopathy

Marcelo Imbroinise Bittencourt et al. Ricardo Mourilhe-Rocha

In recent years, we have witnessed a significant shift in the management of symptomatic Hypertrophic Cardiomyopathy (HCM). For decades, treatment relied on medications that provided hemodynamic support without directly addressing sarcomeric hypercontractility, the primary pathophysiological driver of the disease. The emergence of Cardiac Myosin Inhibitors (CMIs), particularly mavacamten and aficamten, has transformed this landscape.^, In an article published in this issue of the International Journal of Cardiovascular Sciences, Fogaça PHT et al. present an updated systematic review and meta-analysis that reinforces the efficacy of this class of medications while providing important insights into their effects in both obstructive and non-obstructive HCM.

The study pooled data from six randomized controlled trials. Five included patients with obstructive HCM, whereas one – the MAVERICK-HCM trial – included patients with non-obstructive HCM.^,,- The inclusion of non-obstructive patients represents a distinctive aspect of this analysis, as the benefits of CMIs in the absence of left ventricular outflow tract (LVOT) obstruction remain less well established.

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ABCHF

Original Article

Unrecognized Chronic Kidney Disease and the Therapeutic Gap in Outpatients with Heart Failure and Reduced Ejection Fraction

Felipe Lopes Grillo et al. Julia Rosembach Bruscato Felipe Storm Ross Eduardo Zanetti Bergamaschi … Gabriel Della Torres Marinho Juliana Berndt Nunes Rosane Carolina Paes De Lira Lidia Ana Zytynski Moura

Abstract

Background

Chronic kidney disease (CKD) is common in heart failure with reduced ejection fraction (HFrEF), but its true prevalence may substantially exceed formal diagnosis, contributing to undertreatment with guideline-directed medical therapy (GDMT).

Objectives

To determine the prevalence of unrecognized CKD in an HFrEF outpatient clinic, compare optimized medical therapy (OMT) according to renal status and KDIGO stages, and identify independent predictors of OMT.

Methods

Analytical cross-sectional study including 469 patients with HFrEF (LVEF ≤ 40%) followed between 2019–2022 with calculable eGFR (CKD-EPI 2021). Classification: no CKD (eGFR ≥ 60; n = 307), hidden CKD (eGFR < 60 without documentation; n = 104), and recognized CKD (formal documentation; n = 58). OMT was defined as RAAS blockade + beta-blocker + MRA at ≥ 50% of target doses.

Results

CKD affected 34.5% by eGFR, but only 15.1% had documentation – 64% were hidden, predominantly G3a (82%) and G3b (64%). OMT followed a monotonic gradient across KDIGO stages: G1 56.5%, G2 48.1%, G3a 38.4%, G3b 24.1%, G4 18.5% (Cochran–Armitage p < 0.001). Spironolactone was the most affected therapy (84.7% vs. 60.3%; p < 0.001). In multivariable analysis, recognized CKD was associated with lower OMT (OR 0.47; 95% CI 0.23–0.92; p = 0.03), along with age (OR 0.95/year; p < 0.001), while diabetes was paradoxically associated with higher OMT (OR 1.90; p = 0.003).

Conclusion

Nearly two-thirds of CKD cases in HFrEF are unrecognized, concentrated in moderate stages where therapeutic benefit is greatest. Routine calculation of eGFR is a simple intervention to reduce this gap.

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ABC

Research Letter

Never Stop Looking – the Heart is Not Always the Answer

Daniel Inácio Cazeiro et al. Diogo Ferreira Lia Bruno Ana Isabel Ferreira … João Leitão Fausto J. Pinto Rui Plácido

Case presentation

A 63-year-old woman presented with a two-year history of worsening fatigue, dyspnea (World Health Organization functional class III), and palpitations. The echocardiogram had demonstrated a high probability of pulmonary hypertension (PH), and she was subsequently referred to a PH expert center. Her past medical history included systemic arterial hypertension, iron deficiency anemia secondary to gastrointestinal bleeding from duodenal telangiectasias (endoscopically treated), and a previous extraforaminal L3-L4 discectomy due to lumbar herniated disk with associated radiculopathy, performed at another hospital two years before the first appointment. The post-operative period was complicated by severe acute anemia of unclear etiology, which required nine red blood cell transfusions.

At the time of referral, the patient was taking furosemide 40 mg once daily (OD), candesartan 16 mg + hydrochlorothiazide 12.5 mg OD, simvastatin 20 mg OD, and alprazolam 0.25 mg OD. She had a history of smoking but no significant occupational exposures, and her family history was unremarkable.

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ABC

Case Report

Systemic Sclerosis Associated Pulmonary Arterial Hypertension with Venous Involvement – a Novel ABCC8 Pathogenic Variant

Daniel Inácio Cazeiro et al. João Cravo Mariana Pereira Silva João R. Inácio … Oana Moldovan Catarina Sousa Catarina Lopes Resende João Eurico Fonseca Fausto J. Pinto Rui Plácido

Discussion

PAH with venous/capillary involvement (formerly referred to as pulmonary veno-occlusive disease [PVOD] /capillary hemangiomatosis) is a rare, severe form of PH, with an incidence of 0.1-0.5 cases/million/year. This condition comprises a fibroproliferative process of pulmonary venous and capillary compartments, with small vein occlusion caused by smooth muscle hypertrophy and collagen deposition.

The diagnosis of PVOD is challenging due to its non-specific presentation, often mimicking PAH. Moreover, histological confirmation via lung biopsy is contraindicated due to the significant risk of hemorrhage. Certain clinical and imaging features can facilitate a presumptive diagnosis, which include typical findings on CCTA – centrilobular ground-glass opacities, septal lines, and mediastinal lymphadenopathy, severely reduced DLCO on PFTs, and low oxygen saturation nadir during the 6MWT. PVOD manifests in two forms: hereditary, which is associated with autosomal recessive biallelic mutations in the EIF2AK4 gene, and sporadic, which presents later in life and more frequently in males. Several risk factors are linked to sporadic PVOD, including prior exposure to chemotherapy (particularly alkylating agents),^, tobacco, and organic solvents such as trichloroethylene.^,

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ABC

Editorial

Cost Implications and Perspectives of TAVI versus SAVR in the Hospital Setting

Renato Paladino Nemoto et al. Roney Orismar Sampaio

The article “Transcatheter Aortic Valve Implantation vs. Aortic Valve Surgery in a Brazilian Public Health System (SUS) Hospital: Periprocedural Outcomes and Costs” addresses a relevant topic, especially after the inclusion of transcatheter aortic valve implantation (TAVI) in the list of procedures available in the SUS. Patients undergoing TAVI are typically older, with more comorbidities, and are more frail. Conversely, surgical aortic valve replacement (SAVR) in elderly patients can result in increased morbidity and length of hospital stay.

In the study, surgical risk was low in both groups (STS 3.62±2.28 in the TAVI group vs 1.64±0.94 in SAVR, p<0.001), which may demonstrate the limitation of surgical risk stratification with current tools. Mortality was lower in the TAVI group (2.8% vs. 5.0%), but without reaching statistical significance. The minimally invasive strategy (without general anesthesia, with transthoracic echocardiography monitoring) resulted in a shorter hospital length of stay (2.0 [1.0; 4.0] days in the TAVI group vs. 8.0 [7.0; 12.0] days in the SAVR group, p<0.001). However, the costs were higher than those of SAVR. The high prices of materials (R$ 55,750.90 [52,345.30; 92,286.8] TAVI vs. R$ 22,518.10 [19,130.60; 25,875.10] SAVR, p<0.001) is a significant factor. Late complications, such as a higher rate of hospital infection, including surgical wound infection, are unfavorable to surgery, due to increased hospitalization for use of antimicrobials, hospital human resources, among other costs.

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ABC

Letter to the Editor

Broadening Insights into Implantable Cardioverter Defibrillator Appropriateness: The Role of Economic and Psychosocial Markers, Cardiomyopathy Subtypes, and Advanced Therapies

Ömer Faruk Yılmaz et al. Yusuf Ziya Şener

Dear Editor,

We read with great interest the article by Carvalho et al. titled “Potentially Inappropriate Cardioverter Defibrillator Implants in Secondary Prevention of Death”, which highlights the critical role of socioeconomic and psychosocial markers (EPSM) in predicting early mortality post-implantable cardioverter defibrillator (ICD) implantation. While the study provides valuable insights into multidisciplinary team (MDT) assessments, we would like to address two significant limitations that could refine future research and clinical practice.

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ABC

Editorial

Why Treat Chronic Forms of Chagas Disease with Benznidazole if Adverse Reactions are Very Frequent?

Alejandro Marcel Hasslocher-Moreno

After the successful control of vector and transfusion transmission of Chagas disease (CD) in Brazil and other endemic countries in Latin America, the current challenge is the control of congenital transmission of the disease. However, we still have a large contingent of people infected with Trypanosoma cruzi in the chronic form, estimated at around 3.7 million individuals in Brazil alone, with approximately 590,000 of them being women of childbearing age.

Two treatment guidelines for CD were produced by the Pan American Health Organization and the Brazilian Ministry of Health in 2018.^, These guidelines define the degrees of recommendation for trypanocidal treatment, with an emphasis on newborns, children and adolescents, women of childbearing age, and adults with the indeterminate clinical form up to 50 years of age. Studies in these populations have proven the efficacy of etiological treatment in the chronic form of CD, which leads to a cure in children, impacts vertical transmission, and reduces the risk of progression of the disease to the cardiac form.^–

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ABC

Review Article

Pathogenesis, Assessment, and Treatment of Coronary Microcirculation Dysfunction

Bing Ji et al. Xue-Bo Liu

Abstract

Cardiovascular disease is the predominant cause of mortality on a global scale. Research indicates that women exhibit a greater likelihood of presenting with non-obstructive coronary artery disease (CAD) when experiencing symptoms of myocardial ischemia in comparison to men. Additionally, women tend to experience a higher burden of symptoms relative to men, and despite the presence of ischemic heart disease, they are frequently reassured erroneously due to the absence of obstructive CAD. In cases of ischemic heart disease accompanied by symptoms of myocardial ischemia but lacking obstructive CAD, it is imperative to consider coronary microvascular dysfunction as a potential underlying cause. Coronary microvascular dysfunction, characterized by impaired coronary flow reserve resulting from functional and/or structural abnormalities in the microcirculation, is linked to adverse cardiovascular outcomes. Lifestyle modifications and the use of anti-atherosclerotic and anti-anginal medications may offer potential benefits, although further clinical trials are necessary to inform treatment strategies. This review aims to explore the prevalence, underlying mechanisms, diagnostic approaches, and therapeutic interventions for coronary microvascular dysfunction.

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IJCS

Review Article

Cardiac Amyloidosis in Women: An Underappreciated Diagnosis

Larissa Neto Espíndola et al. Gláucia Maria Moraes de Oliveira Cláudia Maria Vilas Freire Marildes Luiza de Castro Maria Cristina Costa de Almeida

Abstract

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy that affects the heart mostly in two forms: immunoglobulin light chain amyloidosis (AL-CM) and transthyretin amyloidosis.

Transthyretin amyloid cardiomyopathy (ATTR-CM) predominantly affects the elderly population, mainly men (about 70-80%), and usually manifests with symptoms of heart failure (HF).

Despite technological advances in medicine, CA is still an underdiagnosed condition, especially in women, partly due to the known male predominance and high level of suspicion required for diagnosis. It is important to remember that amyloidosis is a systemic disease with a heterogeneous and non-specific presentation. It’s worth paying attention to the patient’s medical history and red flags in clinical and diagnostic tests (electrocardiogram [ECG], echocardiogram [ECHO], cardiac magnetic resonance [CMR]).

Accurate and timely diagnosis is crucial for appropriate management and prognosis.

So far, the under-representation of women in clinical trials may have also limited the evidence on sex-specific diagnosis, and outcomes.

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ABC

Editorial

The Price of Delay: Socioeconomic Disparities and Diagnostic Oversights in Occlusion Myocardial Infarction Care

José Nunes de Alencar et al. Jesse T. T. McLaren

Acute myocardial infarction with acute coronary occlusion represents the most severe and urgent facet of acute coronary syndromes. Seminal studies have taught us that reestablishing coronary flow in patients with occluded arteries, whether through thrombolysis or primary angioplasty, can alter the natural history of the disease and significantly reduce mortality associated with this syndrome.^,

The authors of “The Clinical and Economic Impact of Delayed Reperfusion Therapy: Real-World Evidence” provide compelling data from a wealthy metropolitan region in Brazil, concluding that each additional hour of delay in reperfusion therapy was associated with a 6.2% increase (95% confidence interval: 0.3% to 11.8%, p = 0.032) in the risk of in-hospital mortality. In addition, overall costs were 45% higher among individuals treated after 9 hours compared to those treated within the first 3 hours, which was mainly due to in-hospital costs (p = 0.005). Gioppatto et al. also note, from other studies, the financial impacts on patients and families due to delayed reperfusion, and they call for ST elevation myocardial infarction (STEMI) networks to address the uneven distribution of percutaneous coronary intervention (PCI)-capable centers.

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ABCHF

Review Article

Particularities of Heart Failure with Preserved Ejection Fraction in Women – Pathways to Better Care

Larissa Neto Espíndola et al. Maria Cristina Costa de Almeida Marildes Luíza de Castro Cláudia Maria Vilas Freire Gláucia Maria Moraes de Oliveira

Abstract

While heart failure with reduced ejection fraction (HFrEF) is more prevalent in males, female predominance is a striking feature in heart failure with preserved ejection fraction (HFpEF).

The incidence of HFpEF has been gaining alarming proportions. It has exceeded HFrEF as the primary form of heart failure, especially in the female sex. Women tend to have smaller cardiac chambers with higher left ventricular ejection fraction; however, they have more severe symptoms and signs. Until now, there is no consensus about the exact mechanisms of these differences related to sex. Understanding these mechanisms is essential to mitigate the risks for HFpEF and direct efforts towards identifying novel preventive and disease-modifying treatments. Lifestyle, pharmacologic, and device-based approaches to reduce the medical and societal impact of HFpEF could improve patients’ quality of life.

The purpose of this review is to outline known biological sex differences in women with HFpEF with a specific focus on pathways to better care for the diagnosis and treatment of women with HFpEF.

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IJCS

Review Article

Bothrops Moojeni Snake Venom: A Source of Potential Therapeutic Agents Against Hemostatic Disorders

Natália Barreira Silva et al. Edigar Henrique Vaz Dias Júnia de Oliveira Costa Carla Cristine Neves Mamede

Abstract

Hemostasis is a complex set of biological processes responsible for blood fluidity within normal vessels and for the physiological interruption of bleeding in cases of vascular injury. Bothrops moojeni snake venom is rich in bioactive compounds of pharmacological and clinical interest since its protein components are capable of interfering with many points of the hemostatic process. Here, we present the B. moojeni venom proteins that affect hemostasis and discuss their pharmacological and clinical potential. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Data were obtained from the CAPES Journal Portal database, using the terms “Bothrops” AND “hemostasis”, in a search for scientific articles made available in the last 20 years. Many components isolated from B. moojeni snake venom are characterized for their effect on hemostasis and possible application in the diagnosis and treatment of hemostatic disorders.

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ABCHF

Review Article

Is Right Ventricular Cardiogenic Shock Important To You?

Marcus Vinícius Santos Andrade et al. Carlos Aurélio Santos Aragão Renato Moraes Pereira Figueiredo Breno Macedo de Almeida Lucas Guimarães da Rocha

Introduction

In the scenario of cardiogenic shock, attention was almost exclusively focused on the left ventricle (LV). Currently the concept that the circulatory system involves the interdependence between the LV and the right ventricle (RV) has been reinforced, and researchers seek to achieve a clearer understanding of the role of the right ventricle in cardiogenic shock.

In the 1940s, in search of a more in-depth understanding of the role of the RV, the American doctor and researcher Isaac Starr and his team carried out a series of experiments on animals, in which they caused severe damage to the right ventricle. Observing only a small increase in peripheral venous congestion, they concluded that “the weakness on the right side of the heart… appears to be less important” in the establishment of heart failure (HF).

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ABCHF

Viewpoint

Rethinking the Definition of Heart Failure Based on Ejection Fraction: Reflections with Impact on Therapy

Marcelo Iorio Garcia

The universal definition of heart failure (HF) has been in a state of constant change in the last decades. It is necessary for the definition to be simple, comprehensible, and easily applied in clinically, as well as capable of differentiating patients’ stages and severity, allowing stratification of levels of care, especially regarding candidates for specific therapies.

In relation to ejection fraction (EF), which is the subject of our reflection, the most recent document proposed the following subdivisions according to left ventricular ejection fraction (LVEF): HF with reduced ejection fraction (HFrEF), EF ≤ 40%; HF with midrange ejection fraction (HFmrEF), EF 41% to 49%; HF with preserved ejection fraction (HFpEF), EF ≥ 50%; and HF with improved EF (HFiEF), HF with EF ≤ 40% that has increased by at least 10 points, with the second measurement reaching > 40%.

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ABCIC

Editorial

Chronic Coronary Syndrome: What to Expect from Investigation and Management After ISCHEMIA?

Lucas Cronemberger Maia Mendes et al. Rafael Willain Lopes Rodrigo Julio Cerci Simone Cristina Soares Brandão

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ABCHF

Review Article

How to Treat Heart Failure in Patients with Cardiac Amyloidosis

Fabiana Goulart Marcondes-Braga et al. Carlos Aurélio dos Santos Aragão

Abstract

Amyloidosis is a multisystem disease characterized by deposition of fibrillar proteins in different tissues, the heart being one of the sites of amyloid deposition. Cardiac amyloidosis may present as a restrictive syndrome with symptoms of heart failure (HF). Treatment includes prognosis-modifying medications in HF; their optimization, however, is a challenge due to the frequent adverse effects in this population. Renin-angiotensin-aldosterone system blockade should be carried out using low doses because, due to autonomic dysfunction, these drugs may cause hypotension and fatigue. The use of diuretics is necessary to maintain euvolemic status and optimized preload; however, due to the ventricular restriction present in cardiac amyloidosis, these medications should be used with caution. In patients with amyloidosis who progress to advanced HF, there are particularities in relation to indications for heart transplantation or long-term ventricular assist devices. The objective of this article is to review the treatment alternatives for HF in patients with cardiac amyloidosis.

Amyloidosis is a multisystem disease characterized by the deposition of fibrillar proteins with specific structural characteristics and a beta-pleated shape. The deposition of these proteins in the heart and the involvement of the autonomic nervous system make it challenging to manage heart failure (HF) in these patients. Given this scenario, This article aims to demonstrate how to manage HF in patients with cardiac amyloidosis.

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ABCHF

Review Article

Heart Failure with Preserved Ejection Fraction and Cardiac Amyloidosis: Implications for Treatment

Luiz Claudio Danzmann et al. João Ricardo Cambruzzi Zimmer Anna Paula Tscheika

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with multiple etiologies and varied phenotypic manifestations. Amyloidosis is a systemic disease that frequently affects the myocardium, and it may represent a specific etiology of HFpEF. The treatment of HFpEF associated with amyloidosis is not based on specific evidence, and the risk of hypotension as an adverse effect of pharmacological management is always a concern. In this context, this review addresses some strategies for controlling circulatory congestion, arrhythmias, cardiac conduction disorders, valvular heart diseases, and treatment of the specific type of amyloidosis based on available evidence as well as the latest recommendations and guidelines for managing cardiac amyloidosis.

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ABC

Review Article

Update on the Treatment of Pulmonary Arterial Hypertension

Caio J. Fernandes et al. Daniela Calderaro Ana Paula Luppino Assad William Salibe-Filho … Luciana Tamie Kato-Morinaga Susana Hoette Bruna Piloto Marcela Araújo Castro Roberta Pontes Lisboa Taysa Antonia Felix da Silva Murillo de Araújo Martins Jose L. Alves-Jr Carlos Jardim Mario Terra-Filho Rogerio de Souza

Abstract

In the last decades, important advances have been made in the treatment of pulmonary arterial hypertension (PAH), a severe, progressive, incurable, and potentially fatal disease. For an adequate therapy, correct hemodynamic diagnosis and etiology classification are fundamental. Many etiologies – rheumatic disease, portal hypertension, congenital heart diseases, schistosomiasis – require specific measures, in addition to drug therapy for PAH. The specific therapy for PAH is based on medications that act on three pathophysiological pathways – prostacyclin, endothelin, and nitric oxide pathways. These drugs have multiple presentations (oral, intravenous, subcutaneous, and inhaled) and have changed the history of PAH. This review presents an overview of drug therapy strategies and different forms and peculiarities of PAH.

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ABC

Original Article

Changes in Medical Management after Coronary CT Angiography

Vânia Mairi Naue et al. Gabriel Camargo Letícia Roberto Sabioni Ronaldo de Souza Leão Lima … Maria Eduarda Derenne Andréa Rocha de Lorenzo Monica Di Calafiori Freire Clério Francisco Azevedo Filho Elmiro Santos Resende Ilan Gottlieb

Abstract

Introduction:

Coronary computed tomography angiography (CCTA) allows for non-invasive coronary artery disease (CAD) phenotyping. There are still some uncertainties regarding the impact this knowledge has on the clinical care of patients.

Objective:

To determine whether CAD phenotyping by CCTA influences clinical decision making by the prescription of cardiovascular drugs and their impact on non-LDL cholesterol (NLDLC) levels.

Methods:

We analysed consecutive patients from 2008 to 2011 submitted to CCTA without previous diagnosis of CAD that had two serial measures of NLDLC, one up to 3 months before CCTA and the second from 3 to 6 months after.

Results:

A total of 97 patients were included, of which 69% were men, mean age 64 ± 12 years. CCTA revealed that 18 (18%) patients had no CAD, 38 (39%) had non-obstructive (< 50%) lesions and 41 (42%) had at least one obstructive ≥ 50% lesion. NLDLC was similar at baseline between the grups (138 ± 52 mg/dL vs. 135 ± 42 mg/dL vs. 131 ± 44 mg/dL, respectively, p = 0.32). We found significative reduction in NLDLC among patients with obstrctive lesions (-18%, p = 0.001). We also found a positive relationship between clinical treatment intensification with aspirin and cholesterol reducing drugs and the severity of CAD.

Conclusion:

Our data suggest that CCTA results were used for cardiovascular clinical treatment titration, with especial intensification seen in patients with obstructive ≥50% CAD.

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