A simplified approach to radiofrequency catheter ablation of idiopathic ventricular outflow tract premature ventricular contractions.

INTRODUCTION: Frequently, low voltage areas (LVAs) and diastolic potentials (DPs) are present at ablation sites in sinus rhythm in patients with idiopathic premature ventricular contractions (PVCs). OBJECTIVE: Validate these findings as substrates for PVCs and evaluate the feasibility of a simplified substrate approach based on LVAs and DPs for ablation of idiopathic outflow tract PVCs, in patients with a low PVC burden during the procedure. METHODS: Prospective single-arm clinical trial at two centers with comparison with a historical group, matched to age and gender. The study group consisted of consecutive patients referred for ablation of frequent idiopathic PVCs with inferior axis, that presented with less than two PVCs/min in first 5 min of the procedure. The ablation was based on fast mapping of the right ventricular outflow tract in sinus rhythm looking for LVAs and DPs, defined as isolated small amplitude potentials occurring after the T wave of the surface echocardiogram. The area with LVAs and DPs was tagged, and a simplified activation mapping of the PVCs was done in that area. The procedure time, success rate, and recurrence rate were compared with the historical group in whom ablation was performed based on activation and pace mapping only. A validation group without PVCs was also studied to assess the prevalence of LVAs and DPs in the general population. RESULTS: The study (n = 38), historical (n = 38), and validation (n = 38) groups did not differ in relation to age or gender. Prevalence of LVAs and DPs was significantly higher in the study group in comparison with the validation group, respectively, 71% versus 11%, p < 0.0001 and 87% versus 8%, p < 0.0001. Procedure time was significantly lower in the study group when comparing to the historical group, 130 (100-164) versus 183 (160-203) min, p < 0.0001 and the success rate was significantly higher, 90% versus 64%, p = 0.013. The recurrence rate in patients with a successful ablation was not significantly different between both groups, Log-rank = 0.125. CONCLUSION: The prevalence of LVAs and DPs was significantly higher in the study group than in the validation group. The proposed approach proved to be feasible, faster, and more efficient than the historical approach.

Validation of an electrocardiographic marker of low voltage areas in the right ventricular outflow tract in patients with idiopathic ventricular arrhythmias.

BACKGROUND: Previous studies have reported the presence of subtle abnormalities in the right ventricular outflow tract (RVOT) in patients with apparently normal hearts and ventricular arrhythmias (VAs) from the RVOT, including the presence of low voltage areas (LVAs). This LVAs seem to be associated with the presence of ST-segment elevation in V1 or V2 leads at the level of the 2nd intercostal space (ICS). OBJECTIVE: Our aim was to validate an electrocardiographic marker of LVAs in the RVOT in patients with idiopathic outflow tract VAs. METHODS: A total of 120 patients were studied, 84 patients referred for ablation of idiopathic VAs with an inferior axis by the same operator, and a control group of 36 patients without VAs. Structural heart disease including arrhythmogenic right ventricular cardiomyopathy was ruled out in all patients. An electrocardiogram was performed with V1-V2 at the 2nd ICS, and ST-segment elevation ≥1 mm and T-wave inversion beyond V1 were assessed. Bipolar voltage map of the RVOT was performed in sinus rhythm (0.5-1.5 mV color display). Areas with electrograms <1.5 mV were considered LVAs, and their presence was assessed. We compared three groups, VAs from the RVOT (n = 66), VAs from the LVOT (n = 18) and Control group (n = 36). ST-elevation, T-wave inversion and left versus right side of the VAs were tested as predictors of LVAs, respective odds ratio (ORs) (95% confidence interval [CI]) and p values, were calculated with univariate logist regression. Variables with a p < .005 were included in the multivariate analysis. RESULTS: ST-segment elevation, T-wave inversion and LVAs were present in the RVOT group, LVOT group and Control group as follows: (62%, 17%, and 6%, p < .0001), (33%, 29%, and 0%, p = .001) and (62%, 25%, and 14%, p < .0001). The ST-segment elevation, T-wave inversion and right-sided VAs were all predictors of LVAs, respective unadjusted ORs (95% CI), p values were, 32.31 (11.33-92.13), p < .0001, 4.137 (1.615-10.60), p = .003 and 8.200 (3.309-20.32), p < .0001. After adjustment, the only independent predictor of LVAs was the ST-segment elevation, with an adjusted OR (95% CI) of 20.94 (6.787-64.61), p < .0001. CONCLUSION: LVAs were frequently present in patients with idiopathic VAs. ST-segment elevation was the only independent predictor of their presence.

Genetic information improves the prediction of major adverse cardiovascular events in the GENEMACOR population.

The inclusion of a genetic risk score (GRS) can modify the risk prediction of coronary artery disease (CAD), providing an advantage over the use of traditional models. The predictive value of the genetic information on the recurrence of major adverse cardiovascular events (MACE) remains controversial. A total of 33 genetic variants previously associated with CAD were genotyped in 1587 CAD patients from the GENEMACOR study. Of these, 18 variants presented an hazard ratio >1, so they were selected to construct a weighted GRS (wGRS). MACE discrimination and reclassification were evaluated by C-Statistic, Net Reclassification Index and Integrated Discrimination Improvement methodologies. After the addition of wGRS to traditional predictors, the C-index increased from 0.566 to 0.572 (p=0.0003). Subsequently, adding wGRS to traditional plus clinical risk factors, this model slightly improved from 0.620 to 0.622 but with statistical significance (p=0.004). NRI showed that 17.9% of the cohort was better reclassified when the primary model was associated with wGRS. The Kaplan-Meier estimator showed that, at 15-year follow-up, the group with a higher number of risk alleles had a significantly higher MACE occurrence (p=0.011). In CAD patients, wGRS improved MACE risk prediction, discrimination and reclassification over the conventional factors, providing better cost-effective therapeutic strategies.

Additional value of a combined genetic risk score to standard cardiovascular stratification.

The utility of genetic risk scores (GRS) as independent risk predictors remains inconclusive. Here, we evaluate the additive value of a multi-locus GRS to the Framingham risk score (FRS) in coronary artery disease (CAD) risk prediction. A total of 2888 individuals (1566 coronary patients and 1322 controls) were divided into three subgroups according to FRS. Multiplicative GRS was determined for 32 genetic variants associated to CAD. Logistic Regression and Area Under the Curve (AUC) were determined first, using the TRF for each FRS subgroup, and secondly, adding GRS. Different models (TRF, TRF+GRS) were used to classify the subjects into risk categories for the FRS 10-year predicted risk. The improvement offered by GRS was expressed as Net Reclassification Index and Integrated Discrimination Improvement. Multivariate analysis showed that GRS was an independent predictor for CAD (OR = 1.87; p<0.0001). Diabetes, arterial hypertension, dyslipidemia and smoking status were also independent CAD predictors (p<0.05). GRS added predictive value to TRF across all risk subgroups. NRI showed a significant improvement in all categories. In conclusion, GRS provided a better incremental value in intermediate subgroup. In this subgroup, inclusion of genotyping may be considered to better stratify cardiovascular risk.

The importance of assessing nutritional status in elderly patients with heart failure.

Heart failure (HF) is a syndrome characterized by high morbidity and mortality, despite advances in medical and device therapy that have significantly improved survival. The outcome of HF in elderly patients results from a combination of biological, functional, psychological, and environmental factors, one of which is nutritional status. Malnutrition, as well as HF, is frequently present with aging. Early detection might lead to earlier intervention. It is our goal to review the importance of nutritional status in elderly patients with HF, as well as tools for assessing it. We also propose a simple decision algorithm for the nutritional assessment of elderly patients with HF.

WITHDRAWN: Impact of genetic information on Coronary Disease risk in Madeira: The GENEMACOR study.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, 10.1016/j.repc.2022.10.005. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Independent association of the variant rs1333049 at the 9p21 locus and coronary heart disease.

INTRODUCTION: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. AIM: To investigate whether the SNP rs1333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. METHODS: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.71 +/- 8.9 years, 79.9% male and 683 controls without coronary disease (mean age 53.3 +/- 10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. RESULTS: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR = 1.33; p = 0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR = 1.34, p = 0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR = 1.05, p = 0.670). After logistic regression analysis, the CC genotype remained in the equation with OR = 1.7; p = 0.018 and CG with OR = 1.5, p = 0.048. CONCLUSION: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.

Interaction of paraoxonase-192 polymorphism with low HDL-cholesterol in coronary artery disease risk.

INTRODUCTION: Coronary artery disease (CAD) is the main cause of mortality in developed countries. Increased lipid peroxidation is associated with accelerated progression of atherosclerosis. Paraoxonase (PON1) is an antioxidant enzyme bound to high-density lipoprotein (HDL), which protects against lipid peroxidation and coronary artery disease. PON1 activity is under genetic control and its molecular basis is a polymorphism in the PON1 gene that shows two common isoforms: the wild Q form (192 Gln) with high ability to protect LDL from lipid peroxidation in vitro, and the mutated R (Arg) form with lower ability. AIM: To explore the interaction of the R allele of the paraoxonase gene and low HDL-cholesterol concentrations in CAD risk. METHODS: The study population consisted of 818 individuals, 298 coronary patients, aged 55.0 +/- 10.3 years, 78.9% male, and 520 age and gender matched healthy controls, aged 53.3 +/- 11.7 years, 72.5% male. Low HDL-cholesterol was defined as < 0.90 mmol/l in men and < 1.11 mmol/l in women. Comparisons of genotypes between cases and controls were performed by a chi-square test. Statistical significance was accepted at p < 0.05. Odds ratios and 95% confidence intervals for the RR genotypes and HDL-deficient subjects were computed using univariate analysis (2 x 2 tables). To determine the interaction between the RR paraoxonase genotype and HDL-deficient subjects, we used 4 x 2 epidemiologic tables and synergy measures: the additive model (Rothman's synergy index, SI) and multiplicative model (Khoury's synergy index, SIM). The relative excess risk due to interaction (RERI) and the attributable proportion (AP) due to interaction (Rothman) were calculated. RESULTS: The PON1 RR192 polymorphism was associated with coronary heart disease (OR = 1.61; p = 0.043) in the whole population. HDL-deficient subjects with the RR192 genotype showed increased risk for CAD (OR = 17.38; p < 0.0001) compared to those with normal HDL and RR192 (OR = 1.39; p = 0.348) and HDL-deficient subjects not carrying the RR genotype (OR = 7.79; p < 0.0001). Synergy measures were SI = 2.3, SIM = 1.6; RERI = 9.2. CONCLUSION: These data suggest the existence of a synergistic effect of the PON1 RR192 genotype (with lower antioxidant ability) and HDL-deficient subjects in risk for development of CAD. The AP due to this interaction was 0.53, meaning that 53% of CAD was explained by this interaction.

Percutaneous aortic valvuloplasty in inoperable symptomatic severe aortic stenosis in the very elderly.

Aortic valve replacement is the first therapeutic option in patients with symptomatic severe aortic stenosis. Given the fact that percutaneous aortic valve implantation is a relatively new procedure and the need for palliative treatment in symptomatic patients with a high surgical risk, percutaneous balloon aortic valvuloplasty is still employed. The authors describe two cases of percutaneous balloon aortic valvuloplasty in very elderly patients with severe calcified aortic stenosis not suitable for cardiac surgery, exacerbated in one case by significant coronary artery disease and left ventricular systolic dysfunction. The authors also review the role of this procedure in current interventional cardiology.

Genetic Risk Analysis of Coronary Artery Disease in a Population-based Study in Portugal, Using a Genetic Risk Score of 31 Variants.

BACKGROUND: Genetic risk score can quantify individual's predisposition to coronary artery disease; however, its usefulness as an independent risk predictor remains inconclusive. OBJECTIVE: To evaluate the incremental predictive value of a genetic risk score to traditional risk factors associated with coronary disease. METHODS: Thirty-three genetic variants previously associated with coronary disease were analyzed in a case-control population with 2,888 individuals. A multiplicative genetic risk score was calculated and then divided into quartiles, with the 1st quartile as the reference class. Coronary risk was determined by logistic regression analysis. Then, a second logistic regression was performed with traditional risk factors and the last quartile of the genetic risk score. Based on this model, two ROC curves were constructed with and without the genetic score and compared by the Delong test. Statistical significance was considered when p values were less than 0.05. RESULTS: The last quartile of the multiplicative genetic risk score revealed a significant increase in coronary artery disease risk (OR = 2.588; 95% CI: 2.090-3.204; p < 0.0001). The ROC curve based on traditional risk factors estimated an AUC of 0.72, which increased to 0.74 when the genetic risk score was added, revealing a better fit of the model (p < 0.0001). CONCLUSIONS: In conclusion, a multilocus genetic risk score was associated with an increased risk for coronary disease in our population. The usual model of traditional risk factors can be improved by incorporating genetic data.

The genetic variant C825T of the beta 3 subunit of G protein is associated with hypertension in a Portuguese population. / A variante genética c825t da subunidade ß3da proteína G associa­se com a hipertensão arterial numa população portuguesa.

INTRODUCTION: Hypertension is an important public health problem, affecting about 25% of the adult population worldwide.1 Genetic and environmental factors contribute to its pathogenesis. The T allele of the C825T polymorphism of the beta 3 subunit of G protein (rs5443) leads to the production of a truncated variant that enhances intracellular signaling and may interfere with the regulation of blood pressure. This genetic variant has been described as a risk factor for hypertension, although study results are controversial. OBJECTIVE: The objective of this study was to analyze the association of the C825T polymorphism of the GNB3 gene with the occurrence of hypertension in a Portuguese population from the Madeira archipelago. METHODS: A case-control study was performed with 1641 Caucasian individuals (mean age 50.6±8.1 years), 848 with hypertension and 793 controls. Blood was collected from all participants for biochemical and genetic analysis, including genotyping of the C825T polymorphism. Logistic regression analysis was performed to determine which variables were significantly associated with the onset of hypertension. Statistical analyses were performed using IBM SPSS version 19.0 and p-values <0.05 were considered statistically significant. RESULTS: In our study, there was a significant association between the C825T polymorphism of the GNB3 gene and the occurrence of hypertension (odds ratio 1.275; 95% confidence interval 1.042-1.559; p=0.018) in the dominant model, after multivariate analysis. CONCLUSION: We conclude that the C825T polymorphism of the beta 3 subunit of G protein is significantly and independently associated with the occurrence of hypertension in the study population.

[Genetic Polymorphisms Associated with the Onset of Arterial Hypertension in a Portuguese Population]. / Polimorfismos Genéticos Associados ao Aparecimento de Hipertensão Arterial Numa População Portuguesa.

INTRODUCTION: Arterial hypertension is a complex, multifactorial disease, controlled by genetic and environmental factors. OBJECTIVE: Evaluate the genetic susceptibility for developing arterial hypertension and its association with the traditional risk factors in the outbreak of this pathology. MATERIAL AND METHODS: Case-control study with 1712 individuals, mean age of 51.0 ± 7.9 years (860 hypertensive patients and 852 controls). Biochemical and traditional risk factors, and genetic variants were evaluated: ACE I/D rs4340, ACE A2350G rs4343, AGT T174M rs4762, AGT M235T rs699 AGTR1 A1166C rs5186, CYP11B2 -344 C/T rs1799998, ADRB1 R389G rs1801253, ADRB2 R16G rs1042713, ADD1 G460W rs4961, SCNN1G G173A rs5718, GNB3 C825T rs5443, ATP2B1 A/G rs2681472, CYP17A1 T/C rs11191548, SLC4A2 C/T rs2303934. The risk of each gene for hypertension was estimated by the dominant, recessive, co-dominant and multiplicative models. By logistic regression, variables associated with hypertension were evaluated. ROC curves were first performed with traditional risk factors and then adding the genetic variants associated with hypertension. Data were analyzed by SPSS for Windows 19.0 and MedCalc v. 13.3.3.0. RESULTS: The genetic variants ADD1 G460W, GNB3 C825T, ACE I/D, ACE A2350G were associated with hypertension. ROC curve with traditional risk factors and these variants showed an increase in the predictive capacity of hypertension (p = 0.018). DISCUSSION: According to the results of our study, the genetic variants found to be associated with hypertension were: ACE I/D rs4340, ACE A2350G rs4343, ADD1 G460W rs4961 and GNB3 C825T rs5443. The first two variants are associated with hypertension by interfering with the renin-angiotensin-aldosterone system, which plays an important role in regulating blood pressure. It should be noted that genes encoding the components of renin-angiotensin-aldosterone system are natural candidates for the development and progression of hypertension. In our population alpha-aducin polymorphism (ADD1 G460W rs4961) was also associated with hypertension. In a Portuguese population, known to have high salt intake, it makes sense that this polymorphism which is relevant in salt and water management may consequently be relevant in the onset of hypertension. The genetic variant GNB3 C825T rs5443 that affects intracellular signalling was also found to be a strong risk candidate for hypertension. Initially, with the elaboration of the ROC curve and calculation of the AUC using only with traditional risk factors and later by adding the variants ADD1 G460W, GNB3 C825T, ACE I/D and ACE A2350G to the traditional risk factors, we verified that genetic polymorphisms increased the predictive risk of hypertension, when compared to the risk given only by traditional risk factors, with statistical significance (p = 0.018). This suggests that hypertension is a multifactorial disease that results from the interaction of environmental, genetic and lifestyle factors that interact with each other and lead to the advent of this important pathology. CONCLUSION: In our study, the hypertension-associated polymorphisms are linked to the renin-angiotensin-aldosterone axis (ACE I/D, ACE A2350G), as well as to salt and water management (ADD1 G460W, GNB3 C825T). Through a multivariate analysis, it was concluded that these two last genetic variants together with four of the traditional risk factors (smoking, alcohol consumption, obesity and diabetes) are associated in a significant and independent way with essential hypertension. In a predictive model of hypertension, the introduction of genetic variants slightly increases the predictive value of the model.

Introdução: A hipertensão arterial é uma doença complexa, multifatorial, controlada por fatores genéticos e ambientais.Objetivo: Avaliar a susceptibilidade genética no aparecimento de hipertensão arterial e sua associação com os fatores de risco tradicionais na eclosão desta patologia.Material e Métodos: Estudo caso-controlo com 1712 indivíduos, idade média de 51,0 ± 7,9 anos (860 hipertensos e 852 controlos). Avaliaram-se os fatores tradicionais, bioquímicos e as variantes genéticas: ACE I/D rs4340, ACE A2350G rs4343, AGT T174M rs4762, AGT M235T rs699 AGTR1 A1166C rs5186, CYP11B2 -344 C/T rs1799998, ADRB1 R389G rs1801253, ADRB2 R16G rs1042713, ADD1 G460W rs4961, SCNN1G G173A rs5718, GNB3 C825T rs5443, ATP2B1 A/G rs2681472, CYP17A1 T/C rs11191548, SLC4A2 C/T rs2303934. Calculámos o risco de cada gene para a hipertensão, pelos modelos dominante, recessivo, co-dominante e multiplicativo. Através da regressão logística, avaliámos as variáveis associadas à hipertensão. Elaboraram-se curvas ROC com os fatores tradicionais e posteriormente adicionando as variantes genéticas associadas com hipertensão. Analisámos os dados através do SPSS for Windows 19.0 e MedCalc v. 13.3.3.0.Resultados: As variantes genéticas ADD1 G460W, GNB3 C825T, ACE I/D e ACE A2350G associaram-se à hipertensão. A curva ROC com os factores de risco tradicionais e estas variantes mostrou um incremento na capacidade preditiva de hipertensão (p = 0,018).Discussão: Segundo os resultados do nosso estudo as variantes genéticas que após análise univariada se associaram à hipertensão arterial foram a ACE I/D rs4340, ACE A2350G rs4343, ADD1 G460W rs4961, GNB3 C825T rs5443. As duas primeiras variantes relacionam-se com a hipertensão arterial por interferirem no sistema renina-angiotensina-aldosterona, que tem um importante papel na regulação da pressão arterial. Salienta-se o facto dos genes que codificam os componentes do sistema renina-angiotensinaaldosterona serem candidatos naturais ao desenvolvimento e progressão da hipertensão arterial. Também na nossa população os polimorfismos da alfa-aducina (ADD1 G460W rs4961), associaram-se à hipertensão arterial. Nesta população portuguesa, conhecida por ter elevado consumo de sal, faz sentido que estes polimorfismos, sejam relevantes na gestão do sal e da água e consequentemente, no aparecimento de hipertensão arterial. A variante genética GNB3 C825T rs5443 que interfere na sinalização intracelular também constituiu uma forte candidata à hipertensão arterial. Com a elaboração da curva ROC e cálculo das AUC inicialmente só com os fatores de risco tradicionais e posteriormente adicionando as variantes ADD1 G460W, GNB3 C825T, ACE I/D e ACE A2350G aos fatores de risco tradicionais, verificámos ter havido um incremento no risco preditivo de hipertensão arterial, relativamente ao existente só com os fatores de risco tradicionais, com significado estatístico (p = 0,018). Isto sugere que a hipertensão arterial é uma doença multifatorial, que resulta da interação de fatores ambientais, genéticos e estilos de vida que interagem entre si e levam ao aparecimento desta importante patologia.Conclusão: No nosso estudo os polimorfismos associados à hipertensão, estão ligados ao eixo renina-angiotensina-aldosterona (ACE I/D, ACE A2350G), bem como à gestão de sal e água (ADD1 G460W, GNB3 C825T). Através de uma análise multivariada, concluiu-se que estas duas últimas variantes genéticas conjuntamente com quatro dos fatores tradicionais (tabagismo, hábitos alcoólicos, obesidade e diabetes) se associam de forma significativa e independente à hipertensão arterial essencial. Num modelo preditivo de hipertensão arterial, a introdução das variantes genéticas aumenta ligeiramente o valor preditivo do modelo.

Furosemide Prescription During the Dry State Is a Predictor of Long-Term Survival of Stable, Optimally Medicated Patients With Systolic Heart Failure.

BACKGROUND: Furosemide is associated with poor prognosis in patients with heart failure and reduced ejection fraction (HFrEF). AIM: To evaluate the association between daily furosemide dose prescribed during the dry state and long-term survival in stable, optimally medicated outpatients with HFrEF. POPULATION AND METHODS: Two hundred sixty-six consecutive outpatients with left ventricular ejection fraction <40%, clinically stable in the dry state and on optimal heart failure therapy, were followed up for 3 years in a heart failure unit. The end point was all-cause death. There were no changes in New York Heart Association class and therapeutics, including diuretics, and no decompensation or hospitalization during 6 months. Furosemide doses were categorized as low or none (0-40 mg/d), intermediate (41-80 mg/d), and high (>80 mg). Cox regression was adjusted for significant confounders. RESULTS: The 3-year mortality rate was 33.8%. Mean dose of furosemide was 57.3 ± 21.4 mg/d. A total of 47.6% of patients received the low dose, 42.1% the intermediate dose, and 2.3% the high dose. Receiver operating characteristics for death associated with furosemide dose showed an area under the curve of 0.74 (95% confidence interval [CI]: 0.68-0.79; P < .001), and the best cutoff was >40 mg/d. An increasing daily dose of furosemide was associated with worse prognosis. Those receiving the intermediate dose (hazard ratio [HR] = 4.1; 95% CI: 2.57-6.64; P < .001) or high dose (HR = 19.8; 95% CI: 7.9-49.6; P < .001) had a higher risk of mortality compared to those receiving a low dose. Patients receiving >40 mg/d, in a propensity score-matched cohort, had a greater risk of mortality than those receiving a low dose (HR = 4.02; 95% CI: 1.8-8.8; P = .001) and those not receiving furosemide (HR = 3.9; 95% CI: 0.07-14.2; P = .039). CONCLUSION: Furosemide administration during the dry state in stable, optimally medicated outpatients with HFrEF is unfavorably associated with long-term survival. The threshold dose was 40 mg/d.

Treatment with Optimal Dose Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Has a Positive Effect on Long-Term Survival in Older Individuals (Aged >70 Years) and Octogenarians with Systolic Heart Failure.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is a disease of older people, but the target doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are unknown. OBJECTIVE: To evaluate the association of ACEI/ARB dose level with long-term survival in stable older patients (aged >70 years) and octogenarian outpatients with HFrEF. POPULATION AND METHODS: A total of 138 outpatients aged >70 years (35.5 % > 80 years), with an LVEF <40 % and who were clinically stable on optimal therapy were followed up for 3 years. The ACEI/ARB doses were categorized as: none (0), low (1-50 % target dose), and high (50-100 % target dose). The Cox regression survival model was adjusted for age, ischemic etiology, and renal function. RESULTS: ACEIs/ARBs were prescribed to 91.3 % of patients, and 52.9 % received the high dose. Survival improved with increasing ACEI/ARB dose level in the total population (Hazard Ratio [HR] = 0.67; 95 % confidence interval [CI] 0.55-0.82; p < 0.001), older patients aged >70 years (HR = 0.65; 95 % CI 0.51-0.83; p < 0.001), and octogenarians (HR = 0.71; 95 % CI 0.51-0.99; p = 0.045). The low (HR = 0.35; 95 % CI 0.16-0.76; p = 0.008) and high doses (HR = 0.13; 95 % CI 0.06-0.32; p < 0.001) improved survival compared with not receiving ACEIs/ARBs. The high dose was associated with a better survival than the low dose in the total population (HR = 0.35; 95 % CI 0.19-0.67; p = 0.001) and in a propensity score-matched cohort (HR = 0.41; 95 % CI 0.16-1.02; p = 0.056). In octogenarians, all dose levels were associated with improved survival compared with not receiving ACEIs/ARBs, but there was no difference between ACEI/ARB doses. CONCLUSION: The achieved optimal dose of ACEIs/ARBs in ambulatory older people with HFrEF is associated with long-term survival.

Usefulness of Doppler myocardial imaging for identification of mutation carriers of familial hypertrophic cardiomyopathy.

Because myocyte dysfunction and disarray are early abnormalities in hypertrophic cardiomyopathy (HC), we tested if Doppler myocardial imaging (DMI) could identify systolic and diastolic dysfunction in mutation carriers (MC) (genotype positive patients without hypertrophy, defined as phenotype negative after conventional screening tests). In a single family with a missense mutation in the myosin binding protein C gene (Arg 502 Gln) we identified 5 MCs; these subjects were asymptomatic and had normal physical examination, normal electrocardiogram, treadmill stress test, ambulatory Holter electrocardiogram, and normal conventional M-mode, 2-dimensional, and Doppler echocardiography. In each patient we performed a DMI study and measured the peak velocities of the systolic (S), rapid filling (E), and atrial contraction (A) waves in the 4 sides of the mitral annulus, in 8 left ventricular segments (apical views), in the tricuspid annulus, and in 2 right ventricular segments. These data were compared with those from 10 normal volunteers matched for sex, age, and body surface. Compared with the normal volunteers, the MCs had lower left ventricular systolic velocities and higher right ventricular systolic velocities; lower diastolic rapid filling velocities; higher or similar atrial contraction velocities; reduced E/A; lower percentage of annular sides and segments with E/A >1 and lower average number of sides and/or segments with E/A >1 per patient; similar right ventricular rapid filling velocities; and similar or higher atrial contraction wave velocities. Thus, DMI detects important left and right ventricular annular and regional myocardial contraction and relaxation abnormalities independently of the presence of hypertrophy, in HC. These results show that DMI is more sensitive than conventional echocardiography and establishes a new and highly accurate method for the noninvasive screening of MCs of the disease.

Doppler tissue imaging: regional myocardial function in hypertrophic cardiomyopathy and in athlete's heart.

BACKGROUND: The distinction between hypertrophic cardiomyopathy (HCM) and the athlete's (AT) heart is an important clinical problem, and the analysis of regional myocardial function with Doppler tissue imaging may be useful in the differential diagnosis. OBJECTIVE: Our aim was to compare regional function assessed by Doppler tissue imaging in rowers and in a group of patients with HCM. METHODS: In 24 patients with nonobstructive HCM and in 20 competitive rowers with similar age, blood pressure, and heart rate, we analyzed with pulsed Doppler tissue imaging left ventricular (LV) regional function (velocities, time intervals, heterogeneity and asynchrony indices, and meridional gradient) in the longitudinal (8 segments, apical views) and in the radial (2 segments, short-axis view) axis. RESULTS: Compared with AT, patients with HCM showed: (1). systolic function; (a). longitudinal: lower velocities and meridional gradient; longer precontraction period (PCP); and higher PCP/LV contraction time; (b). radial: lower velocities and gradient; longer PCP; and higher PCP/LV contraction time; (2.diastolic function; (a). logitudinal: lower e (early diastolic), a (late diastolic), and e/a velocities; and longer prerelaxation time and time to peak e. The percentage of segments with e/a < 1 was 25% in the HCM group and 0% in the AT heart group; (b). radial: lower e velocity and gradient; lower e/a gradient; and longer medial prerelaxation and basal time to peak e. Most of these differences also occurred in the nonhypertrophied inferior wall of patients with HCM. CONCLUSIONS: There are significant differences between regional LV function of competitive rowers and patients with HCM. These differences (1). occur in systole and diastole; (2). affect velocities and time intervals; (3). are more striking in the long axis, but are also seen in the short axis, and (4). also occur in nonhypertrophied segments, suggesting the usefulness of the technique in the differential diagnosis between the 2 situations, namely in individuals that fall in Maron's "grey zone."

Tissue Doppler imaging assessment of long axis left ventricular function in hypertensive patients with concentric left ventricular hypertrophy: differential diagnosis with hypertrophic cardiomyopathy.

BACKGROUND: The differential diagnosis between hypertrophic cardiomyopathy and hypertensive heart disease has clinical, therapeutic and prognostic implications, but is not always easy with conventional echocardiography. Tissue Doppler imaging of the mitral annulus allows the detailed study of long axis left ventricular function in hypertrophic cardiomyopathy and may be useful in the differential diagnosis. METHODS: 23 patients with non-obstructive hypertrophic cardiomyopathy and 25 hypertensive patients with concentric left ventricular hypertrophy with similar age, body surface and heart rate were studied with pulsed tissue Doppler imaging of the 4 sides of the mitral annulus (septal, lateral, inferior, anterior) in 4 and 2 chamber views. In each wave (systolic-s, rapid filling-e, atrial contraction-a) we analyzed velocities, time intervals and velocity-time integrals, as well as heterogeneity and asynchrony. Data were compared among the different sides in each group, between groups and with conventional Doppler data. RESULTS: In contrast to hypertensive patients, hypertrophic cardiomyopathy patients showed: 1--Systolic function: lower "s" wave velocities and integrals, higher systolic heterogeneity, longer isovolumic relaxation time and higher PEP/LVET (pre ejection period/left ventricular ejection time). 2--Diastolic function: lower "e" and "a" wave, higher "a" and "e/a" heterogeneity index, higher percentage of annular sides with e/a > or = l, longer isovolumic relaxation time and time to peak e, and higher diastolic asynchrony. Some of these abnormalities occurred in annular sides adjacent to non-hypertrophied walls. CONCLUSIONS: This study shows that: 1--Long axis systolic and diastolic left ventricular function are significantly different between hypertrophic cardiomyopathy patients and hypertensive patients with concentric left ventricular hypertrophy. 2--These functional differences occur in the velocity domain (with heterogeneity), in the time domain (with asynchrony) and also in velocity time integrals. 3--Long axis systolic and diastolic dysfunction occur in annular sides contiguous to hypertrophied and non-hypertrophied walls, enhancing the role of tissue Doppler imaging in the differential diagnosis between these diseases.

Tissue Doppler imaging assessment of long axis left ventricular function in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy is classically defined as a diastolic disease with normal systolic function. Long axis left ventricular function is an important and sensitive determinant of global ventricular function but its assessment is often difficult and complex. Tissue Doppler imaging of the mitral annulus allows the study of long axis left ventricular function. METHODS: 47 patients with non-obstructive hypertrophic cardiomyopathy and 45 healthy volunteers, matched by age and sex, were studied with pulsed tissue Doppler imaging of the 4 sides of the mitral annulus (septal, lateral, inferior, anterior) in 4 and 2 chamber views. In each wave (systolic-s, rapid filling-e, atrial contraction-a) we analyzed velocities, time intervals and velocity-time integrals, as well as heterogeneity and asynchrony. Data were compared among the different sides in each group, between groups and with conventional Doppler data. RESULTS: In contrast to normal subjects, hypertrophic cardiomyopathy patients showed: 1--Systolic function: lower velocities, longer systolic time intervals (isovolumic relaxation time, time to peak s, ejection time), higher systolic asynchrony (time to peak s, ejection time, systolic time) and lower s/shortening fraction ratio. These changes occurred despite normal indices of global systolic function. 2--Diastolic function: lower velocities (much lower rapid filling velocity, lower atrial contraction velocity, lower septal e/a), higher e/a heterogeneity index, longer protodiastolic times (isovolumic relaxation time and time to peak e), higher diastolic asynchrony (time to peak e) and lower e wave integral. Hypertrophic cardiomyopathy patients also showed higher average number of annular sides with e/a < 1 per patient and higher percentage of e/a < 1, mainly on the septal side. CONCLUSIONS: This study shows that: 1--Tissue Doppler imaging allows the detailed analysis of long axis left ventricular function in hypertrophic cardiomyopathy patients. 2--Long axis systolic function is abnormal in this disease, even in the presence of normal indices of global systolic function. 3--Long axis diastolic function is deeply disturbed in hypertrophic cardiomyopathy, at ventricular and atrial levels. 4--Long axis dysfunction occurs in annular sides contiguous to hypertrophied and non-hypertrophied walls, highlighting the role of other factors in its pathophysiology.

Risk factors and clinical angiographical characteristics of myocardial infarction in women.

INTRODUCTION: Myocardial infarction has a higher incidence in men. However, in women, although less frequent, it has a worse prognosis. OBJECTIVE: With the present work we aim to define the clinical and angiographical characteristics and evolution of myocardial infarction in women compared with men. METHODOLOGY: We studied 235 sequential inpatients with acute myocardial infarction in the Intensive Care Unit who underwent post-infarction catheterization. We then compared female with male patients in terms of risk factors, location and type of infarction, coronary morphology and post-infarction complications. RESULTS: About 22% of the patients hospitalized following myocardial infarction were female. The women were older than the men (65.9 +/- 11.2 vs. 60.3 +/- 11.9; p < 0.01), and had a higher prevalence of high blood pressure (71% vs. 54%, p < 0.05) and a lower prevalence of smoking (19% vs. 50%, p < 0.001). Post-infarction angina was more frequent in women (50% vs. 23%, p < 0.001). Neither Q-wave versus non-Q wave myocardial infarction nor its location were significantly different between the sexes. In terms of coronary morphology, myocardial infarction without significant lesions was more frequent in women (10% vs. 3%, p < 0.05) and there were no significant.

Regional myocardial function by tissue Doppler in hypertrophic cardiomyopathy: the impact of obstruction.

BACKGROUND: The conventional echocardiographic assessment of myocardial function in patients with obstructive hypertrophic cardiomyopathy (HOCM) is complex, because of the load dependency of this method. Tissue Doppler imaging (TDI) may improve this evaluation. AIM: To compare regional myocardial function with TDI, between patients with hypertrophic obstructive cardiomyopathy (HOCM) and with non-obstructive forms of the disease (NOHCM). METHODS: 26 patients with HOCM and 23 with NOHCM were studied with pulsed TDI. We studied longitudinal (8 left ventricular segments, apical views) and radial regional function (2 segments, short axis view), and analyzed velocities, time intervals, velocity-time integrals and heterogeneity and asynchrony indices and the meridional (basal-medial segments) velocity gradient in each wall. Data were compared within each group and between groups. RESULTS: Compared to NOHCM, HOCM patients showed: systolic functions: a) longitudinal: similar velocities, time intervals and integrals; b) radial: higher meridional gradient, lower velocity-time integrals. Diastolic function: a) longitudinal: lower a, higher e and e/a tendency; lower e meridional gradient, higher percentage of septal and anterior wall segments with e/a > or = 1; b) radial: lower a velocities and integrals, shorter diagnostic time. CONCLUSIONS: This study shows that in HOCM patients, the presence of obstruction and its associated load conditions have a different impact on systolic and diastolic regional myocardial function, in long and short axis, assessed with TDI. So, in HOCM patients: 1-Long axis regional systolic function is similar to the non-obstructive forms, suggesting relative load independence. 2-Long and short axis regional diastolic function is, in specific segments and parameters, different from the non-obstructive forms. These data should be taken into account in the assessment of regional myocardial function with TDI in HOCM.