Use of disease-modifying drugs in diabetic patients with heart failure with reduced ejection fraction.

Type 2 diabetes mellitus and heart failure are closely related, patients with type 2 diabetes mellitus have a higher risk of developing heart failure, and those with heart failure are at increased risk of developing type 2 diabetes. Although no specific randomized clinical trials have been conducted to test the effect of cardiovascular therapies (drugs and/or devices) in diabetic patients with heart failure, a lot of evidence shows that all interventions effective in improving prognosis in patients with heart failure reduced ejection fraction are equally beneficial in patients with and without diabetes. However, the use of disease-modifying drugs in patients with diabetes and heart failure reduced ejection fraction is a clinical challenge due to the increased risk of adverse effects. For example, ß-blockers are underutilized in diabetic patients due to the theoretical unfavorable effects on glucose metabolism as well as the use of drugs that interact with the renin-angiotensin system can be challenged in patients with diabetic nephropathy because of the risk of hyperkalemia. This review outlines the current use of disease-modifying drugs in diabetic patients with heart failure reduced ejection fraction. In addition, the role of novel pharmacologic agents as type 2 sodium-glucose co-transporter inhibitors (SGLT2ii) is discussed.

Genome Editing and Heart Failure.

Heart failure is a leading and growing cause of morbidity and mortality worldwide and clinically is defined by the presence of typical symptoms and signs due structural or functional cardiac abnormalities. In addition to family history of heart failure, genetic predisposition to cardiomyopathies and exposure to cardiotoxic agents, risk factors for heart failure with reduced ejection fraction are the same as for chronic coronary syndrome. Genome editing technologies can provide the tools to correct genetic defects responsible for various diseases, including cardiomyopathies. These technologies aim to reverse specific mutations. The same methods can also be applied to modulate and improve heart function. This chapter will briefly explain the pathophysiological and genetic aspects of heart failure and then discuss the clinical applications of genome editing in patients with heart failure.

Natural history of left ventricular hypertrophy in infants of diabetic mothers.

BACKGROUND: This study sought to describe the characteristics and the natural course of left ventricular hypertrophy (LVH) in a well-characterized consecutive cohort of infants of diabetic mothers (IDMs). METHODS: Sixty consecutive IDMs with LVH have been retrospectively identified and enrolled in the study. All IDMs were evaluated at baseline and every 6 months until LV wall thickness regression, defined as the decrease of wall thickness measurement into the normal reference range for cardiac parameters (z-score > -2 and < 2). A comprehensive assessment was performed in those patients with diagnostic markers suggestive of a different cause and/or without significant reduction of the LVH during follow-up. RESULTS: At 1-year follow-up, all IDMs showed a significant reduction of maximal wall thickness MWT (6.00 mm [IQR 5.00-712] vs. 5.50 mm [IQR 5.00-6.00], p-value <0.001; MWT-z-score: 4.86 [IQR 3.93-7.61] vs. 1.72 [IQR 1.08-2.85], p-value <0.001) compared to baseline, and all patients showed LV wall thickness regression or residual mild or moderate LVH (57%, 28%, and 12%, respectively), except 2 patients with persistent severe LVH, that after a comprehensive clinical-genetic assessment were diagnosed as Noonan syndrome with multiple lentigines. At multivariate analysis, MWT was negatively associated with LV wall thickness regression at 1-year follow-up (MWT-mm: OR 0.48[0.29-0.79], p-value = 0.004; MWT-z-score: OR 0.71[0.56-0.90], p-value = 0.004). CONCLUSIONS: LVH in IDMs represents a benign condition with complete regression during the first years of life. In those patients without LV wall thickness regression, combined with clinical markers suggesting a specific disease, a complete work-up is required for a definite diagnosis.

Hemodynamic Effects of Levosimendan in Outpatients With Advanced Heart Failure: An Echocardiographic Pilot Study.

ABSTRACT: Infusions of levosimendan delivered in ambulatory/outpatient settings have been shown to improve quality of life and reduce hospitalizations in patients with advanced heart failure (HF). The aim of this pilot study was to evaluate the effects of ambulatory infusion of levosimendan on echocardiographic markers of perfusion, congestion, and cardiovascular efficiency. Thirty patients with diagnosed advanced HF underwent ambulatorial infusion of levosimendan at a total dose of 6.25 mg as a part of a repetitive biweekly treatment strategy with the inotrope. Standardized transthoracic echocardiography and Doppler examinations, were performed 1 hour before and 48 hours after completion of ambulatory infusion. At 48 hours after ambulatory infusion of levosimendan, a significant increase in the stroke volume (37.47 ± 12.38 mL/beat vs. 45.47 ± 14.48 mL/beat; P < 0.05) and cardiac output (2.64 ± 0.66 L/min vs. 3.26 ± 0.57 L/min; P < 0.05) occurred. Significant postreductions versus prereductions were also recorded in left atrial pressure (27.37 ± 6.62 mm Hg vs. 22.82 ± 4.17 mm Hg; P < 0.01), mean pulmonary artery pressure (27.69 ± 4.64 mm Hg vs. 23.24 ± 5.32; P < 0.01), and inferior vena cava diameter (23.81 ± 7.63 mm vs. 18.53 ± 4.82 mm; P < 0.01). Significant improvements were noted in the resting cardiac power output (0.46 ± 0.15 watt vs. 0.53 ± 0.22 watt; P < 0.01) and the resting cardiac power index (0.24 ± 0.08 watt/m2 vs. 0.28 ± 0.11 watt/m2; P < 0.01). In outpatients with advanced HF, infusion of levosimendan was associated with hemodynamic responses that may contribute to the clinical benefit previously reported in such patients.

The Risk of Sudden Unexpected Cardiac Death in Children: Epidemiology, Clinical Causes, and Prevention.

"Sudden unexplained death (SUD) is a tragic event for both the family and community, particularly when it occurs in young individuals. Sudden cardiac death (SCD) represents the leading form of SUD and is defined as an unexpected event without an obvious extracardiac cause, occurring within 1 hour after the onset of symptoms. In children, the main causes of SCD are inherited cardiac disorders, whereas coronary artery diseases (congenital or acquired), congenital heart diseases, and myocarditis are rare. The present review examines the current state of knowledge regarding SCD in children, discussing the epidemiology, clinical causes, and prevention strategies."

Echocardiography in Advanced Heart Failure for Diagnosis, Management, and Prognosis.

Advanced heart failure, an end-stage disease characterized by high mortality and morbidity despite standard medical therapy, requires various therapeutic strategies like heart transplant and long-term mechanical circulatory support. Echocardiography is the main imaging technique to identify transitions to advanced stages of disease and guide risk stratification and therapeutic decision-making processes. Progressive development of advanced echocardiographic techniques allows more comprehensive assessment of the hemodynamic and structural profiles of patients with advanced heart failure, and its use in clinical practice continues to expand. This article provides an overview of basic and emerging echocardiographic tools to assess patients with advanced heart failure.

Advanced Heart Failure in Special Population-Pediatric Age.

Heart failure (HF) is an important health care issue in children because of its considerable morbidity and mortality. Advanced HF encompasses patients who remained symptomatic despite optimal medical treatment and includes patients who require special management, such as continuous inotropic therapy, mechanical circulatory support, or heart transplantation (HT). HT is the gold standard for children with advanced HF; nonetheless, the number of suitable donors has not increased for decades, leading to prolonged waitlist times and increased mortality rates. Therefore, the role of pediatric mechanic circulatory support has been assessed as an alternative treatment in patients in whom heart transplant could not be performed. The authors discuss the epidemiology, causes, pathophysiology, clinical manifestation, medical treatment, device therapy, and HT in pediatric HF, and a particular emphasis was posed on patients with advanced HF.

Troponin T Mutation as a Cause of Left Ventricular Systolic Dysfunction in a Young Patient with Previous Surgical Correction of Aortic Coarctation.

Coarctation of the aorta is a leading cause of morbidity and mortality among adults with congenital heart disease (ACHD). Lifelong surveillance is mandatory to screen for possible long-term cardiovascular events. Left ventricular systolic dysfunction has been reported in association with recoarctation, and association with dilated cardiomyopathy (DCMP) is very rare. Herein, we report the case of a 19-year-old boy with coarctation of the aorta who complained of mild exertional dyspnea. Cardiac magnetic resonance revealed a moderately dilated, hypokinetic left ventricle (LV), with mildly reduced EF (45%), and residual isthmic coarctation was excluded. Genetic tests revealed a heterozygous missense variant in TNNT2 (NM_001001430.2): c.518G>A (p. Arg173Gln). This case highlights the role of careful history taking: a family history of cardiomyopathy should not be overlooked even when the clinical setting seems to suggest a predisposition to hemodynamic factors for LVSD.

Hypertrophic Cardiomyopathy in Children: Pathophysiology, Diagnosis, and Treatment of Non-sarcomeric Causes.

Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by left ventricular hypertrophy not solely explained by abnormal loading conditions. Despite its rare prevalence in pediatric age, HCM carries a relevant risk of mortality and morbidity in both infants and children. Pediatric HCM is a large heterogeneous group of disorders. Other than mutations in sarcomeric genes, which represent the most important cause of HCM in adults, childhood HCM includes a high prevalence of non-sarcomeric causes, including inherited errors of metabolism (i.e., glycogen storage diseases, lysosomal storage diseases, and fatty acid oxidation disorders), malformation syndromes, neuromuscular diseases, and mitochondrial disease, which globally represent up to 35% of children with HCM. The age of presentation and the underlying etiology significantly impact the prognosis of children with HCM. Moreover, in recent years, different targeted approaches for non-sarcomeric etiologies of HCM have emerged. Therefore, the etiological diagnosis is a fundamental step in designing specific management and therapy in these subjects. The present review aims to provide an overview of the non-sarcomeric causes of HCM in children, focusing on the pathophysiology, clinical features, diagnosis, and treatment of these rare disorders.

Potential role of imaging markers in predicting future disease expression of arrhythmogenic cardiomyopathy.

Aim: To evaluate the predictive accuracy of trabecular hypertrophy/derangement and late gadolinium enhancement in predicting diagnosis of arrhythmogenic cardiomyopathy (AC). Materials & methods: Fifty-nine suspected AC patients were evaluated. To evaluate the ability of these markers to detect patients fulfilling definite diagnosis at 4-year follow-up, sensitivity (Se), specificity (Sp), positive and negative predictive value (PPV and NPV) and predictive accuracy (PA) were calculated. Results: Presence of trabecular hypertrophy/derangement showed high NPV, while late gadolinium enhancement at cardiac MRI high Sp, NPV and PA. Their combination with symptoms and/or revised Task Force Criteria showed a high Sp, NPV and PA for definitive diagnosis during follow-up. Conclusion: In suspected AC patients, the absence of these markers allows to identify those with lower risk of disease progression.

Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies.

Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.

Combined PTPN11 and MYBPC3 Gene Mutations in an Adult Patient with Noonan Syndrome and Hypertrophic Cardiomyopathy.

In this report, an atypical case of Noonan syndrome (NS) associated with sarcomeric hypertrophic cardiomyopathy (HCM) in a 33-year-old patient was described. Genetic testing revealed two different disease-causing mutations: a mutation in the PTPN11 gene, explaining NS, and a mutation in the MYBPC3 gene, known to be associated with HCM. This case exemplifies the challenge in achieving a definite etiological diagnosis in patients with HCM and the need to exclude other diseases mimicking this condition (genocopies or phenocopies). Compound heterozygous mutations are rare but possible in HCM patients. In conclusion, this study highlights the important role of genetic testing as a necessary diagnostic tool for performing a definitive etiological diagnosis of HCM.

Management of pregnancy in cardiomyopathies and heart failure.

Pregnancy exposes women with inherited cardiomyopathies to increased risk for arrhythmias and heart failure. In asymptomatic patients with inherited cardiomyopathies, pregnancy is generally well tolerated. Preconception evaluation, risk assessment and proper counseling by a team of experienced physicians are mandatory in managing women with inherited cardiomyopathies planning pregnancy. In this paper, we reviewed the clinical course, risk assessment and management during pregnancy of women with cardiomyopathies.

Genetics of Takotsubo Syndrome.

Takotsubo syndrome (TTS) is an enigmatic disease with a multifactorial and still unresolved pathogenesis. A genetic predisposition has been suggested based on the few familial TTS cases. Conflicting results have been published regarding the role of functional polymorphisms in relevant candidate genes, such as α1-, ß1-, and ß2-adrenergic receptors; G protein-coupled receptor kinase 5; and estrogen receptors. Further research is required to help clarify the role of genetic susceptibility in TTS.