Progression of Left Ventricular Dysfunction and Remodelling under Optimal Medical Therapy in CHF Patients: Role of Individual Genetic Background

Background. Neurohormonal systems play an important role in chronic heart failure (CHF). Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV) remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, β1adrenergic receptor (AR) Arg389Gly, β2AR Arg16Gly, and β2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (P = .003 and P = .002, respectively) but not of LV ejection fraction (LVEF); β1AR389 GlyGly was related to improvement of LVEF (P = .02) and LV end-systolic volume (P = .01). The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (P < .05 for all). Conclusions. ACE I/D and β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment

Proof of concept study on coronary microvascular function in low flow low gradient aortic stenosis

ObjectivesWe hypothesised that low flow low gradient aortic stenosis (LFLGAS) is associated with more severe coronary microvascular dysfunction (CMD) compared with normal-flow high-gradient aortic stenosis (NFHGAS) and that CMD is related to reduced cardiac performance. MethodsInvasive CMD assessment was performed in 41 consecutive patients with isolated severe aortic stenosis with unobstructed coronary arteries undergoing transcatheter aortic valve implantation (TAVI). The index of microcirculatory resistance (IMR), resistive reserve ratio (RRR) and coronary flow reserve (CFR) were measured in the left anterior descending artery before and after TAVI. Speckle tracking echocardiography was performed to assess cardiac function at baseline and repeated at 6 months. ResultsIMR was significantly higher in patients with LFLGAS compared with patients with NFHGAS (24.1 (14.6 to 39.1) vs 12.8 (8.6 to 19.2), p=0.002), while RRR was significantly lower (1.4 (1.1 to 2.1) vs 2.6 (1.5 to 3.3), p=0.020). No significant differences were observed in CFR between the two groups. High IMR was associated with low stroke volume index, low cardiac output and reduced peak atrial longitudinal strain (PALS). TAVI determined no significant variation in microvascular function (IMR: 16.0 (10.4 to 26.1) vs 16.6 (10.2 to 25.6), p=0.403) and in PALS (15.9 (9.9 to 26.5) vs 20.1 (12.3 to 26.7), p=0.222). Conversely, left ventricular (LV) global longitudinal strain increased after TAVI (-13.2 (8.4 to 16.6) vs -15.1 (9.4 to 17.8), p=0.047). In LFLGAS, LV systolic function recovered after TAVI in patients with preserved microvascular function but not in patients with CMD. ConclusionsCMD is more severe in patients with LFLGAS compared with NFHGAS and is associated with low-flow state, left atrial dysfunction and reduced cardiac performance

Left ventricular chamber dilation and filling pressure may help to categorise patients with type 2 diabetes

Type 2 diabetes may alter cardiac structure and function. Many patients with type 2 diabetes have diastolic dysfunction with preserved ejection fraction (EF). Recently, this latter measure was criticised. Thus, this research looked at the impact of left ventricular end-diastolic volume and E/e' ratio variations in patients with type 2 diabetes and preserved EF with the aim to recognise different clinical phenotypes

Nonalcoholic Fatty Liver Disease Is Associated With Ventricular Arrhythmias in Patients With Type 2 Diabetes Referred for Clinically Indicated 24-Hour Holter Monitoring

Recent studies have suggested that nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of heart rate-corrected QT interval prolongation and atrial fibrillation in patients with type 2 diabetes. Currently, no data exist regarding the relationship between NAFLD and ventricular arrhythmias in this patient population

Heart valve calcification in patients with type 2 diabetes and nonalcoholic fatty liver disease

PurposeAortic valve sclerosis (AVS) and mitral annulus calcification (MAC) are two powerful predictors of adverse cardiovascular outcomes in patients with type 2 diabetes, but the aetiology of valvular calcification is uncertain. Nonalcoholic fatty liver disease (NAFLD) is an emerging cardiovascular risk factor and is very common in type 2 diabetes, but whether NAFLD is associated with valvular calcification in this group of patients is presently unknown.MethodsWe undertook a cross-sectional study of 247 consecutive type 2 diabetic outpatients with no previous history of heart failure, valvular heart diseases (aortic stenosis, mitral stenosis, moderate or severe aortic and mitral regurgitation) or hepatic diseases. Presence of MAC and AVS was detected by echocardiography. NAFLD was diagnosed by ultrasonography.ResultsOverall, 139 (56.3%) patients had no heart valve calcification (HVC-0), 65 (26.3%) patients had one valve affected (HVC-1) and 43 (17.4%) patients had both valves affected (HVC-2). 175 (70.8%) patients had NAFLD and the prevalence of this disease markedly increased in patients with HVC-2 compared with either HVC-1 or HVC-0 (86.1% vs. 83.1% vs. 60.4%, respectively; p&lt;0.001). NAFLD was significantly associated with AVS and/or MAC (unadjusted-odds ratio 3.51, 95%CI 1.89–6.51, p&lt;0.001). Adjustments for age, sex, waist circumference, smoking, blood pressure, hemoglobin A1c, LDL-cholesterol, kidney function parameters, medication use and echocardiographic variables did not appreciably weaken this association (adjusted-odds ratio 2.70, 95%CI 1.23-7.38, p&lt;0.01).ConclusionsOur results show that NAFLD is an independent predictor of cardiac calcification in both the aortic and mitral valves in patients with type 2 diabetes

Stress ossidativo ed infiammazione: basi fisiopatologiche per un nuovo approccio terapeutico nello scompenso cardiaco. Risultati di due trials randomizzati, controllati con placebo.

Introduzione: Lo scompenso cardiaco (SC) si definisce come una complessa condizione fisiopatologica di cronico deterioramento dei meccanismi ossidativi. In pazienti con SC cronico le concentrazioni sieriche di acido urico sono frequentemente elevate e l\u2019iperuricemia riflette un\u2019alterazione del metabolismo ossidativo ed iperattivazione dell\u2019enzima xantina ossidasi (XO). Uno studio clinico recente evidenzia una forte correlazione tra acido urico e parametri ecocardiografici di disfunzione diastolica, condizione di frequente riscontro in pazienti con cardiomiopatia dilatativa e associata a prognosi peggiore. Lo SC, inoltre, rappresenta uno stato infiammatorio caratterizzato da iperproduzione di citochine pro-infiammatorie implicate nella patogenesi di alcuni aspetti tipici dello SC, quali l\u2019edema polmonare acuto. Pregressi studi hanno evidenziato effetti benefici del trattamento con statine in fase di stabilit\ue0 clinica di questa patologia. Scopo: valutare se l\u2019inibizione della XO con allopurinolo possa influire sulle propriet\ue0 diastoliche del miocardio e sui livelli sierici di NT-proBNP in un gruppo di pazienti con SC cronico (Studio di SC cronico); valutare l\u2019effetto del trattamento precoce con statine sul rimodellamento ventricolare sinistro e sui sintomi in un gruppo di pazienti con SC acuto (Studio di SC acuto). Metodi: (Studio di SC cronico): sono stati arruolati 53 pazienti con scompenso cardiaco secondario a cardiomiopatia dilatativa in condizioni cliniche stabili e terapia medica ottimale da almeno 3 mesi e randomizzati in doppio cieco ad allopurinolo 300 mg/die (A), o placebo (P) per 3 mesi. I pazienti sono stati sottoposti ad una valutazione clinica ed ecocardiografico completa all\u2019inizio ed al termine del periodo di trattamento. (Studio di SC acuto): 61 pazienti con disfunzione ventricolare sinistra, ricoverati per episodio di SC acuto, sono stati randomizzati in doppio cieco ad atorvastatina 20mg/die (A), o placebo (P) per 3 mesi. Ciascun paziente \ue8 stato sottoposto a prelievo per ematochimici, valutazione clinica ed esame ecocardiografico completo all\u2019inizio, ad una settimana ed al termine del periodo di studio. Risultati: (Studio di SC cronico): l\u2019et\ue0 media era 66\ub110; la classe NYHA era 2.2\ub10.6; i livelli sierici medi di acido urico erano 400\ub1100mmol/L. Al termine del trimestre di trattamento i livelli sierici di NT-proBNP si sono ridotti nel gruppo A (-191\ub1583 mmol/L, p=0.0004), con un significativo effetto terapeutico (p=0.0033), mentre non si sono modificati nel gruppo P. E\u2019 stata riscontrata un riduzione significativa della velocit\ue0 dell\u2019onda E mitralica nel gruppo A (0.6\ub10.2 vs. 07\ub10.2 m/s, p=0.01), ma non nel gruppo P ed il rapporto E/E\u2019 \ue8 migliorato nel gruppo A (10.7\ub16.7 vs. 15.1\ub111.8), mentre \ue8 rimasto stabile nel gruppo P, con un significativo effetto terapeutico per entrambi (p=0.01 and p=0.02 rispettivamente). (Studio di SC acuto): all\u2019inizio dello studio le caratteristiche cliniche ed ecocardiografiche non differivano nei 2 gruppi di pazienti (et\ue0 media 72\ub17 anni gruppo P; 68\ub112 anni gruppo A; Colesterolo 3.6\ub11 mmol/L gruppo P; 3.5\ub11.3 mmol/L gruppo A; FE 29\ub17 % gruppo P; 25\ub16 % gruppo A). Al follow up la classe NYHA e lo score di congestione sono migliorati in entrambi i gruppi, tuttavia maggiormente ed in assenza di un peggioramento della funzione renale nel gruppo A. Si \ue8 evidenziata una riduzione dei volumi ventricolari, in particolare del volume tele-sistolico (\uf044 3 mesi 26 ml; p=0.001) e la FE (\uf044 3 mesi: -5; p=0.0005) \ue8 migliorata solamente nel gruppo A. Infine nello stesso gruppo \ue8 emersa una riduzione significativa del volume atriale sinistro (\uf044 3 mesi: 12.7 ml; p=0.05) ed i parametri di funzione diastolica sono migliorati. Conclusioni: in pazienti con SC il trattamento con allopurinolo in aggiunta alla terapia medica ottimale per tre mesi, apporta un beneficio significativo sui parametri di funzione diastolica ventricolare ed il suo utilizzo correla con una riduzione statisticamente significativa del NT-proBNP. Il trattamento precoce con statina in pazienti con SC acuto migliora i sintomi e influisce sul processo di rimodellamento ventricolare sinistro migliorando FE e riducendo i volumi.Background: Heart failure (HF) is a complex pathophysiological condition of chronic deterioration of oxidative mechanisms. Hyperuricemia, a common finding in this context, reflects the degree of oxidative stress. It has been previously shown that diastolic dysfunction, which is frequently observed in patients with dilated cardiomyopathy and is associated with poor prognosis, relates to serum uric acid levels. Furthermore, HF represents an inflammatory state characterized by overproduction of pro-inflammatory cytokines involved in the pathogenesis of some typical aspects of HF, such as pulmonary oedema. Previous studies showed positive effects of statin treatment in a stable phase of the disease. Aim of the project: to determine whether inhibition of XO with allopurinol might affect diastolic function and NT-proBNP levels in a group of patients with chronic HF (Chronic HF Study); to evaluate the effects of statin therapy on left ventricular (LV) remodeling and symptoms in a group of subjects in the early stage of acute HF (Acute HF Study). Methods: Chronic HF study: 53 stable chronic HF outpatients with LV systolic dysfunction on optimal background therapy and clinically stable for at least three months, were randomly assigned to receive allopurinol (A), 300 mg/day, or placebo (P) for three months, in a double-blind trial. Every patient underwent a complete clinical and echocardiographic evaluation at baseline and at the end of the study. Acute HF study: 61 patients, admitted to our clinic for acute HF episode, with left ventricular dysfunction, were randomized to receive Atorvastatin (A) 20 mg/day or placebo (P) for three months, in a double-blind trial. A biochemical and clinical examination and a complete echocardiogram was performed for each patient at baseline, at one week and at the end of the study period. Results: Chronic HF study: mean age was 66\ub110 years and mean NYHA class was 2.2\ub10.6; mean serum uric acid levels were 400\ub1100 mmol/L. At follow-up, in the allopurinol group there was a significant reduction in NT-proBNP levels compared with baseline (-191\ub1583 mmol/L, p=0.0004), while no significant difference was observed in the placebo group, with a significant treatment effect (p=0.0033). In the allopurinol group there was a significant reduction of mitral E wave velocity (E) (0.6\ub10.2 vs. 07\ub10.2 m/s, p=0.01), and of the ratio between E and the velocity of early myocardial lengthening (E\u2019) (10.7\ub16.7 vs. 15.1\ub111.8), but no significant changes of these two parameters in the placebo group, with a significant treatment effect for both (p=0.01 and p=0.02, respectively). Acute HF study: the two groups did not differ in clinical and echocardiographic baseline characteristics (mean age 72\ub17 years group P; 68\ub112 years group A; Colesterol 3.6\ub11 mmol/L group P; 3.5\ub11.3 mmol/L group A; EF 29\ub17 % group P; 25\ub16 % group A). At follow up NYHA class and congestion score improved in both groups, however more and without worsening of renal function in group A. There was a reduction in LV volumes, in particular in end-systolic volume (\uf044 3 months 26 ml; p=0.001) and EF improved (\uf044 3 months: -5; p=0.0005) only in the Atovarstatin group. Furthermore, in the same group there was a reduction of left atrium volume (\uf044 3 months: 12.7 ml; p=0.05) and diastolic parameters improved. Conclusions: in CHF patients, the addition of allopurinol on top of optimal medical therapy for three months significantly improves echocardiographic parameters of diastolic function and lowers NT-proBNP levels. Early statin treatment in acute HF patients improves symptoms and affects cardiac remodeling by improving EF and reducing LV volumes

Irreversible left atrium dilatation preceding left ventricular dysfunction during trastuzumab therapy

Irreversible left atrium dilatation preceding left ventricular dysfunction during trastuzumab therap

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Background. Neurohormonal systems play an important role in chronic heart failure (CHF). Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV) remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, β1adrenergic receptor (AR) Arg389Gly, β2AR Arg16Gly, and β2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (P = .003 and P = .002, respectively) but not of LV ejection fraction (LVEF); β1AR389 GlyGly was related to improvement of LVEF (P = .02) and LV end-systolic volume (P = .01). The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (P &lt; .05 for all). Conclusions. ACE I/D and β1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment

Impaired Aortic Valve Growth in Type 1 Diabetes Mellitus

The study have evaluated the differences in aortic valve dimensione between type 1 diabetic patients and control subjects. As reported in Table 1, females affected by type 1 diabetes showed an aortic annulus diameter of 9.9 0.9 mm/m2 compared with 11.7 1.1 mm/m2 in female controls (P &lt; 0.01), whereas diabetic males presented a diameter of 10.1 1.1 mm/m2 compared with 11.9 1.4 mm/m2 (P &lt; 0.01) in male controls. Interestingly, men with type 1 diabetes showed a significantly lower aortic annulus diameter than female controls. Moreover, when we compared subjects with the onset of diabetes earlier than 10 years of age (n \ubc 31) and then compared them with those with the onset of the disease later than 22 years of age (n \ubc 19), a tendency towards a lower annulus diameter in patients with an early onset of diabetes (9.8 0.9 vs 10.6 1.1 mm/m2 , respectively; P \ubc 0.07) was observed