Septal Ablation Versus Surgical Myomectomy for Hypertrophic Obstructive Cardiomyopathy.

PURPOSE OF REVIEW: Patients with hypertrophic cardiomyopathy (HCM) who have left ventricular outflow tract obstruction (LVOTO) often experience severe symptoms and functional limitation. Relief of LVOTO can be achieved by two invasive interventions, i.e., surgery myectomy and alcohol septal ablation (ASA), leading in experienced hands to a dramatic improvement in clinical status. Despite extensive research, however, the choice of the best option in individual patients remains challenging and poses numerous clinical dilemmas. RECENT FINDINGS: Invasive strategies have been recently incorporated in recommendations for the diagnosis and treatment of HCM on both sides of the Atlantic. These guidelines are based on a bulk of well-designed but retrospective studies as well as on expert opinions. Evidence now exists that adequate evaluation and management of HCM requires a multidisciplinary team capable of choosing the best available options. Management of LVOTO still varies largely based on local expertise and patient preference. Following the trend that has emerged for other cardiac diseases amenable to invasive interventions, the concept of a "HCM heart team" is coming of age.

Multiple hormonal and metabolic deficiency syndrome in chronic heart failure: rationale, design, and demographic characteristics of the T.O.S.CA. Registry.

Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by "Federico II" University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF.

Management of immunosuppression and antiviral treatment before and after heart transplant for HIV-associated dilated cardiomyopathy.

Infection with HIV may lead to the development of cardiomyopathy as improved antiretroviral regimens continue to prolong patient life. However, advanced therapeutic options, such as heart transplant, have until recently been precluded to HIV-positive persons. A favorable long-term outcome has been obtained after kidney or liver transplant in HIV-positive recipients fulfilling strict virological and clinical criteria. We recently reported the first heart transplant in a HIV-infected patient carried out in our center. In this article, we detail the major challenges we faced with the management of antiretroviral and immunosuppressive treatments over the first 3 years post-transplant. The patient had developed dilated cardiomyopathy while on antiretroviral treatment with zidovudine, lamivudine and efavirenz. He was in WHO Stage 1 of HIV infection and had normal CD4+ count and persistently undetectable HIV-RNA. In spite of cardiac resynchronization therapy and maximal drug therapy, the patient progressed to end stage heart failure, requiring heart transplant. He was placed on a standard immune suppressive protocol including cyclosporine A and everolimus. Despite its potential pharmacokinetic interaction with efavirenz, everolimus was chosen to reduce the long-term risk of opportunistic neoplasia. Plasma levels of both drugs were monitored and remained within the target range, although high doses of everolimus were needed. There were no infectious, neoplastic or metabolic complications during a 3-year follow-up. In summary, our experience supports previous data showing that cardiac transplantation should not be denied to carefully selected HIV patients. Careful management of drug interactions and adverse events is mandatory.

Heart failure: molecular, genetic and epigenetic features of the disease.

Factors that compete to establish heart failure (HF) are not completely known. In the last years the several technological improvements allowed us to deeply study the molecular and genetic aspects of this complex syndrome. This new approach to HF based on molecular biology new discoveries shows us more clearly the pathophysiological bases of this disease, and a future scenery where the genetics may be useful in the clinical practice, as screening of high risk populations, as well as in the diagnosis and therapy of underlying myocardial diseases. The purpose of this review was to analyse the molecular, genetic and epigenetic factors of HF. We described the molecular anatomy of the sarcomere and the pathogenesis of the heart muscle diseases, abandoning the previous monogenic theory for the concept of a polygenic disease. Different actors play a role to cause the illness by themselves, modifying the expression of the disease and, eventually, the prognosis of the patient.

Masked hypertension in young patients after successful aortic coarctation repair: impact on left ventricular geometry and function.

Life expectancy is still reduced in aortic coarctation (AoC) patients despite a successful repair because of late arterial hypertension and atherosclerosis. Masked hypertension (MH) consists of an elevated daytime or awake ambulatory blood pressure (BP) in the presence of a normal BP on conventional measurement at the office. To assess the prevalence of MH among AoC normotensive young patients successfully treated and to evaluate the impact of MH on left ventricular (LV) geometry and function.We studied 76 AoC patients (mean age 14.5±5.7 years, male 64%). According to 24 h ambulatory BP monitoring (ABPM) our sample was divided in real normotensive patients (Group RN, n=40) and MH patients (Group MH, n=36). There was an increased pressure gradient in the aortic arch (15 mm Hg±4 vs 13 mm Hg±4.7, P<0.05), increased LV mass (51 g m(-2.7)±13 vs 46 g m(-2.7)±12, P<0.05), in MH AoC patients. Regional longitudinal deformation properties of the basal septal segment (-15%±2.4 vs -20%±5, P<0.01) and LV twist values (14°±1.6 vs 12°±1.9, P<0.0001) were reduced in the MH group. There is a high prevalence of MH in young patients with repaired AoC, which is associated with abnormal LV structure and function. Clinicians should consider 24 h ABPM measurements in apparently normotensive patients followed up for AoC repair.

Use of NaCl saline hydration and N-Acetyl Cysteine to prevent contrast induced nephropathy in different populations of patients at high and low risk undergoing coronary artery angiography.

AIM: Contrast-induced nephropathy (CIN) is most commonly defined as acute renal failure occurring within 48-72 h of exposure to intravascular radiographic contrast medium that is not attributable to other causes. In international literature a 25% increase in serum creatinine levels or an increase in absolute values of 0.5 mg/dL from baseline has been suggested to define CIN. The reported incidence of CIN varies widely, ranging from 2% to 50%. This variability results from differences in the presence or absence of risk factors. With a retrospective analysis authors evaluated the use of NaCl saline hydration and N-acetyl cysteine (NAC) to prevent CIN in different populations of patients at high and low risk undergoing coronary artery angiography. METHODS: From January 2007 to December 2008, 597 patients underwent coronary artery angiography with a low osmolarity contrast agent. Nephrotoxic drugs such as diuretics, metformin, ACE-I and ARBs were stopped at least 24 h before the procedure. The population was divided into two groups: group A (high risk 342 patients, 57.2%) identified for the presence of at least one risk factor such as diabetes, age >65 years, baseline creatinine >1.4 mg/dL and group B (low risk 255 patients, 42.8%) for the absence of any of the risk mentioned above. Only group A was treated with a saline hydration (1 mL/kg/h) plus NAC 600 mg 12 h before and 12 h after the procedure. RESULTS: The overall incidence of CIN was 6.7% (40 patients). In particular, the incidence of CIN was 4.4% (15 patients) in the group A and 9.8% (25 patients) in the group B respectively (P=0.017). Interestingly, the Contrast Index (volume administrated/theoretical maximum volume) was significantly lower in group B (P<0.005). In the multivariate analysis, including risk factors such as age, diabetes, hypertension, hypercholesterol-mia, current smoke, baseline creatinine level, Contrast Index and hydration, the last variable was the only one inversely correlated independently with the incidence of CIN (P=0.001). CONCLUSIONS: The hydration with saline and NAC is an effective and low-cost tool in preventing CIN in patients undergoing coronary artery angiography and, according to the current guidelines, should be used in all high-risk patients. Present results show that even in patients at low risk for CIN, hydration could be useful: in fact, despite the Contrast Index was significantly lower in this population, the incidence of CIN was greater, thus suggesting a potential role for hydration also in the low-risk population.

A child cohort study from southern Italy enlarges the genetic spectrum of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiovascular disorder worldwide. It is the leading cause of sudden cardiac-related death in young people and a major cause of cardiac failure and death in elderly people. However, HCM frequently goes undiagnosed until the appearance of overt signs and symptoms, thereby delaying prophylactic and therapeutic measures. We screened patients for sarcomeric genes associated with HCM to obtain information that could be useful for an early diagnosis and so limit the severe consequences of silent HCM. We recruited 39 families with HCM from southern Italy and found mutations in 41% of families (12 with familial HCM and 4 with sporadic HCM). The remaining 23 families (59%) were negative for myofilament gene mutations. Of the 12 mutations identified, 8 were novel. Screening of the other family members available revealed that 27 had mutations; 11 of these individuals had no signs or symptoms suggestive of HCM. This study, besides characterizing the spectrum of mutations in another childhood population, and revealing an even greater genetic heterogeneity than formerly recognized, may increase genotype-phenotype correlations, and thus may help to identify asymptomatic candidates for early preventive or therapeutic measures.

Novel insights into the role of cardiotrophin-1 in cardiovascular diseases.

Cardiotrophin-1 (CT-1), a member of interleukin (IL)-6 family, was originally isolated for its ability to induce a hypertrophic response in neonatal cardiac myocytes. This cytokine mediates a pleiotropic set of growth and differentiation activities through a unique receptor system, consisting of IL-6 receptor (IL-6R) and a common signal transducer, the glycoprotein 130 (gp130). Both in humans and in mice, CT-1 mRNA has been detected in several tissues, such as liver tissue, adipose tissue, and tissues in the respiratory and nervous systems; in each of these tissues it performs different functions. Predominant actions of CT-1 are on the heart, where it is synthesized and where it provides first myocardial protection by promoting cell survival and proliferation, it carries on its haemodynamic effects and endocrine properties, and finally, it predisposes the heart to pathological conditions. The aim of this review is to describe the pathophysiological mechanisms through which CT-1 carries out its activities, especially on the heart, and its potential contribution as a disease marker in clinical cardiology. Recent studies have confirmed its active role in promoting structural changes typical of most common cardiovascular disease, such as hypertension, valve diseases, congestive heart failure, and coronary artery disease. In fact, CT-1 induces myocyte hypertrophy and collagen synthesis, thereby participating in the progression of ventricular remodelling, which results in cardiac muscle failure at the latest stage. CT-1 plasma levels are elevated in patients with hypertension and coronary artery diseases, and they are also correlated with the severity of valve diseases and heart failure. Therefore, CT-1 may represent a diagnostic, staging, and prognostic biomarker of cardiovascular diseases.

Left atrial myocardial function in either physiological or pathological left ventricular hypertrophy: a two-dimensional speckle strain study.

BACKGROUND: Atrial function is an integral part of cardiac function that is often neglected. The presence of left ventricule hypertrophy (LVH) due to arterial hypertension may impair atrial function. However, it has also been suggested that physical training attenuates the age-associated impairment of diastolic filling. This study investigated whether mechanical dysfunction in the left atrium (LA) is present in patients with either physiological or pathological LVH, using two-dimensional strain rate imaging (2D strain echocardiography; 2DSE). METHODS: Standard echocardiography, exercise stress echo and 2DSE of the left atrium were performed in 40 patients with arterial hypertension, 45 age-matched elite athletes (>40 years) and 25 healthy sedentary controls. Atrial longitudinal strain was performed from the apical views for the basal segments of the LA septum, lateral wall and roof. RESULTS: LV mass index and ejection fraction were comparable between patients with either physiological or pathological LVH. Elite athletes showed increased LV end-diastolic diameter, end-diastolic volume and stroke volume, whereas circumferential end-systolic stress was higher in patients with hypertension. LA diameter and maximum volume were increased but similar between the two groups of patients with LVH. LA active emptying volume and fraction were both higher in patients with hypertension. Conversely, peak systolic myocardial atrial strain was significantly reduced in patients with pathological LVH compared with controls and athletes for all the analysed atrial segments (p<0.0001). Using multivariate analysis, LV end-diastolic volume/body surface area (BSA) (beta coefficient 0.52; p<0.0001) and LV mass (beta = 0.48; p<0.001) in athletes emerged as the only independent determinants of LA lateral wall peak systolic strain. In contrast, in patients with hypertension, an independent negative association of LA lateral wall peak systolic strain with both LV mass (beta = -0.42; p<0.001) and circumferential end-systolic stress (beta = -0.43; p<0.001) was found. In addition, in the overall population of patients with LVH, LA lateral wall systolic strain (beta = 0.49; p<0.0001) was a powerful independent predictor of maximum workload during exercise testing. CONCLUSIONS: 2DSE represents a promising, non-invasive, simple and reproducible technique to assess LA myocardial function in patients with either physiological or pathological LVH. LA myocardial deformation is impaired in patients with hypertension compared with age-matched sedentary controls and elite athletes, and is closely associated with functional capacity during effort.

[The role of natriuretic peptides in heart failure]. / Ruolo dei peptidi natriuretici nello scompenso cardiaco.

Over the last decades, there has been a significant increase in incidence and prevalence of heart failure, a major cause of cardiac morbidity and mortality. Measurements of neurohormones, in particular B-type natriuretic peptide (BNP), can significantly improve diagnostic accuracy, and also correlate with long-term morbidity and mortality in patients with chronic heart failure presenting to the emergency department. BNP is secreted by cardiac ventricles mainly in response to wall stress and neurohormonal factors like the sympathetic nervous system, endothelins, and the rennin-angiotensin-aldosterone system. BNP increases myocardial relaxation and oppose the vasoconstrictive, sodium retaining, and natriuretic effects caused by vasoconstrictive factors. BNP is the first biomarker to prove its clinical value for the diagnosis of left ventricular systolic and diastolic dysfunction but also for the right ventricular dysfunction, guiding prognosis and therapy management. Emerging clinical data will help further refine biomarker-guided therapeutic and monitoring strategies involving BNP.

Subclinical hypothyroidism and Down's syndrome; studies on myocardial structure and function.

BACKGROUND: The management of subclinical hypothyroidism (SH) is still controversial, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut. Some authors have shown abnormalities of myocardial function and structure in adults with SH, which could be reversed by L-thyroxine therapy. As SH frequently affects children with Down's syndrome (DS), and almost one half of these are affected by congenital heart disease, a concomitant SH related impairment of cardiac function might further compromise their clinical condition. AIMS: To establish whether SH influences myocardial structure and function in children with DS. METHODS: Sixteen children with DS and untreated SH and 25 matched euthyroid controls with DS underwent echocardiographic analysis of left ventricular mechanics and tissue characterisation. RESULTS: None of the 16 patients had myocardial impairment. CONCLUSION: Results suggest that children with DS who have SH are not at risk of cardiac disease. Clinicians should consider these data in the management of SH, as the benefit to risk ratio of prolonged L-thyroxine therapy is not clear cut.

Risk factors for pacemaker implantation following aortic valve replacement: a single centre experience.

OBJECTIVE: To identify perioperative clinical predictors of permanent pacemaker implantation following aortic valve replacement. DESIGN AND PATIENTS: Prospective cohort study on 276 patients submitted for aortic valve replacement: 267 patients (mean (SD) age, 57.5 (14) years) with no conduction disturbances, and nine patients (67.7 (5) years) with severe conduction disturbances requiring permanent pacing; 65 perioperative variables (38 preoperative, eight intraoperative, and 19 postoperative) were considered. RESULTS: Nine patients (3.2%) had irreversible second or third degree atrioventricular (AV) block requiring permanent pacing. Risk factors for permanent pacing identified by univariate analysis were: preoperative: additional valvar disease, aortic regurgitation, myocardial infarction, pulmonary hypertension, anaemia, use of digitalis; intraoperative: cardiac arrest; postoperative: cardiac arrest, conduction disturbances, electrolytic imbalance, angiotensin converting enzyme inhibitor use. Multivariate logistic regression analysis identified preoperative aortic regurgitation (p < 0.005; odds ratio (OR) 6.6, 95% confidence interval (CI) 1.6 to 12.2), myocardial infarction (p < 0.0005; OR 15.2, 95% CI 6.3 to 19.9), pulmonary hypertension (p < 0.005; OR 12.5, 95% CI 3.2 to 18.3), and postoperative electrolyte imbalance (p < 0.01; OR 4.5, 95% CI 1.3 to 6.4). CONCLUSIONS: Irreversible AV block requiring permanent pacemaker implantation is an uncommon condition following aortic valve replacement. Previous aortic regurgitation, myocardial infarction, pulmonary hypertension, and postoperative electrolyte imbalance should be considered in order to identify patients at increased risk for advanced AV block.

Risk predictors of paroxysmal atrial fibrillation following aortic valve replacement.

BACKGROUND: Atrial fibrillation (AF) is the most frequently encountered arrhythmic complication associated with cardiac surgery. The aim of this paper was to identify the clinical predictors of AF occurrence following aortic valve replacement. METHODS: Three hundred and two patients were included in this study and divided into two groups according to the absence (SR group, 243 patients, mean age 55.6 +/- 15 years) or the evidence (AF group, 59 patients, mean age 63.8 +/- 11 years) of post-aortic valve replacement AF. Sixty-five perioperative variables (37 preoperative, 8 intraoperative and 20 postoperative) were considered. RESULTS: Post-aortic valve replacement paroxysmal AF occurred in 59 out of 302 patients (19%). At univariate analysis, post-aortic valve replacement AF was associated with advanced age, left atrial enlargement, preoperative episodes of paroxysmal AF, the use of a warm blood cardioplegic solution and normothermia, administration of inotropic agents, prolonged assisted ventilation but also with postoperative acidosis, electrolyte imbalance and atrioventricular and intraventricular conduction disorders. Stepwise forward multivariate logistic regression analysis identified age (p = 0.002, odds ratio--OR 1.04), left atrial enlargement (p = 0.004, OR 2.6), a prior history of paroxysmal AF (p = 0.0003, OR 10.9), and postoperative electrolyte imbalance (p = 0.01, OR 2.3) as independent correlates of AF, whereas the use of hypothermia appeared to be a protective factor (p = 0.0004, OR 0.26). CONCLUSIONS: According to our findings, post-aortic valve replacement AF seems to be associated with well-defined anatomical and electrical substrates generated by advanced age, increased left atrial dimensions, and a possible electrical remodeling consequent to prior repetitive episodes of paroxysmal AF. On these grounds, external factors such as postoperative electrolyte imbalance might enhance atrial ectopic activity and trigger postoperative sustained tachyarrhythmias, while the use of hypothermia might allow for better protection of the atrial myocardium against intraoperative ischemia.

Noninvasive evaluation of arterial abnormalities in young patients with neurofibromatosis type 1.

Neurofibromatosis regroups at least two different autosomal dominant genetic disorders: neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). Vascular disease is an underestimated complication of NF1. Few studies are available on this, all based on case reports. Neurofibromin, NF1 protein product, has also been detected in aortic smooth muscle. The purpose of this study was to evaluate the physical properties of the vessels, by measuring the carotid-femoral pulse wave velocity (PWV). This parameter was assessed by the Complior, a new noninvasive, validated device, used to screen a large population. The authors studied 64 neurofibromatosis patients (34 boys and 30 girls) with a mean age of 12 years (range 5-25 years). To investigate the presence of vascular lesions, aortic stiffness was evaluated by carotid-femoral PWV by using an automatic processor (Complior). They compared data from the PWV with a control group (30 healthy children, 17 boys and 13 girls, mean age 11 years, range 5-23 years). The calculated mean PWV in the control group was 6.5 +/- 1.15 m/s. The mean PWV of the 64 young patients with NF1 was 6.3 +/- 1.02 m/s. There was no difference between the two groups (p=0.39). Nevertheless, analysis of the linear regression has shown a linear relationship between systolic blood pressure (SBP) and PWV in the control group, while in NF1 patients this relationship is not present. The authors suggest that the coexistence of different factors, such as intimal proliferation, thinning media, fragmentation of the elastic tissue, irregularity, stenosis and tortuosity of the vessels, dysplasia of the small vessels, that counterbalance PWV, normalize the mean value. They emphasize the importance of a careful vascular evaluation, using noninvasive method, such as Complior. This device is well accepted by NF1 patients.