Atrial natriuretic peptide stimulates autophagy/mitophagy and improves mitochondrial function in chronic heart failure.

Mitochondrial dysfunction, causing increased reactive oxygen species (ROS) production, is a molecular feature of heart failure (HF). A defective antioxidant response and mitophagic flux were reported in circulating leucocytes of patients with chronic HF and reduced ejection fraction (HFrEF). Atrial natriuretic peptide (ANP) exerts many cardiac beneficial effects, including the ability to protect cardiomyocytes by promoting autophagy. We tested the impact of ANP on autophagy/mitophagy, altered mitochondrial structure and function and increased oxidative stress in HFrEF patients by both ex vivo and in vivo approaches. The ex vivo study included thirteen HFrEF patients whose peripheral blood mononuclear cells (PBMCs) were isolated and treated with αANP (10-11 M) for 4 h. The in vivo study included six HFrEF patients who received sacubitril/valsartan for two months. PBMCs were characterized before and after treatment. Both approaches analyzed mitochondrial structure and functionality. We found that levels of αANP increased upon sacubitril/valsartan, whereas levels of NT-proBNP decreased. Both the ex vivo direct exposure to αANP and the higher αANP level upon in vivo treatment with sacubitril/valsartan caused: (i) improvement of mitochondrial membrane potential; (ii) stimulation of the autophagic process; (iii) significant reduction of mitochondrial mass-index of mitophagy stimulation-and upregulation of mitophagy-related genes; (iv) reduction of mitochondrial damage with increased inner mitochondrial membrane (IMM)/outer mitochondrial membrane (OMM) index and reduced ROS generation. Herein we demonstrate that αANP stimulates both autophagy and mitophagy responses, counteracts mitochondrial dysfunction, and damages ultimately reducing mitochondrial oxidative stress generation in PBMCs from chronic HF patients. These properties were confirmed upon sacubitril/valsartan administration, a pivotal drug in HFrEF treatment.

Chronic Heart Failure Management: Monitoring Patients and Intercepting Exacerbations.

Despite significant progress in the field of therapy and management, chronic heart failure (CHF) still remains one of the most common causes of morbidity and mortality, especially among the elderly in Western countries. In particular, frequent episodes of decompensation and, consequently, repeated hospitalizations represent an unsustainable burden for national health systems and the cause of worsening quality of life. CHF is more prevalent in elderly women, who often have "peculiar" clinical characteristics and a more preserved ejection fraction caused by endothelial dysfunction and micro-vessel damage. At the moment, noninvasive technologies that are able to remotely monitor these patients are not widely available yet, and clinical trials are underway to evaluate invasive remote sensors. Unfortunately, implantable devices for identifying decompensation are not the most practical solution in the majority of of patients with chronic heart failure. In particular, they are hypothesized to have the possibility of monitoring patients by pro-B-type natriuretic peptide, ventricular repolarization variability, and bioimpedance cardiography at the first point of care, but new technology and clinical trials must be planned to address the development and spread of these emergent possibilities.

Effects of sacubitril/valsartan on exercise capacity: a prognostic improvement that starts during uptitration.

PURPOSE: Sacubitril/valsartan is a mainstay of the treatment of heart failure with reduced ejection fraction (HFrEF); however, its effects on exercise performance yielded conflicting results. Aim of our study was to evaluate the impact of sacubitril/valsartan on exercise parameters and echocardiographic and biomarker changes at different drug doses. METHODS: We prospectively enrolled consecutive HFrEF outpatients eligible to start sacubitril/valsartan. Patients underwent clinical assessment, cardiopulmonary exercise test (CPET), blood sampling, echocardiography, and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sacubitril/valsartan was introduced at 24/26 mg b.i.d. dose and progressively uptitrated in a standard monthly-based fashion to 97/103 mg b.i.d. or maximum tolerated dose. Study procedures were repeated at each titration visit and 6 months after reaching the maximum tolerated dose. RESULTS: Ninety-six patients completed the study, 73 (75%) reached maximum sacubitril/valsartan dose. We observed a significant improvement in functional capacity across all study steps: oxygen intake increased, at peak exercise (from 15.6 ± 4.5 to 16.5 ± 4.9 mL/min/kg; p trend = 0.001), while minute ventilation/carbon dioxide production relationship reduced in patients with an abnormal value at baseline. Sacubitril/valsartan induced positive left ventricle reverse remodeling (EF from 31 ± 5 to 37 ± 8%; p trend < 0.001), while NT-proBNP reduced from 1179 [610-2757] to 780 [372-1344] pg/ml (p trend < 0.0001). NYHA functional class and the subjective perception of limitation in daily life at KCCQ-12 significantly improved. The Metabolic Exercise Cardiac Kidney Index (MECKI) score progressively improved from 4.35 [2.42-7.71] to 2.35% [1.24-4.96], p = 0.003. CONCLUSIONS: A holistic and progressive HF improvement was observed with sacubitril/valsartan in parallel with quality of life. Likewise, a prognostic enhancement was observed.

Cardiopulmonary exercise testing and heart failure: a tale born from oxygen uptake.

Since 50 years, cardiopulmonary exercise testing (CPET) plays a central role in heart failure (HF) assessment. Oxygen uptake (VO2) is one of the main HF prognostic indicators, then paralleled by ventilation to carbon dioxide (VE/VCO2) relationship slope. Also anaerobic threshold retains a strong prognostic power in severe HF, especially if expressed as a percent of maximal VO2 predicted value. Moving beyond its absolute value, a modern approach is to consider the percentage of predicted value for peak VO2 and VE/VCO2 slope, thus allowing a better comparison between genders, ages, and races. Several VO2 equations have been adopted to predict peak VO2, built considering different populations. A step forward was made possible by the introduction of reliable non-invasive methods able to calculate cardiac output during exercise: the inert gas rebreathing method and the thoracic electrical bioimpedance. These techniques made possible to calculate the artero-venous oxygen content differences (ΔC(a-v)O2), a value related to haemoglobin concentration, pO2, muscle perfusion, and oxygen extraction. The role of haemoglobin, frequently neglected, is however essential being anaemia a frequent HF comorbidity. Finally, peak VO2 is traditionally obtained in a laboratory setting while performing a standardized physical effort. Recently, different wearable ergo-spirometers have been developed to allow an accurate metabolic data collection during different activities that better reproduce HF patients' everyday life. The evaluation of exercise performance is now part of the holistic approach to the HF syndrome, with the inclusion of CPET data into multiparametric prognostic scores, such as the MECKI score.

ß-Blockers and Erectile Dysfunction in Heart Failure. Between Myth and Reality.

Erectile dysfunction (ED) is a major concern in heart failure (HF) due its high prevalence as well as its negative impact on the quality of life, this condition being usually unrecognized and thus untreated. A number of possible causes might contribute to the above mentioned tight association, i.e., shared risk factors, comorbidities and several physiologic HF abnormalities such as impaired exercise tolerance, psychogenic factors and neurohumoral, metabolic and vascular changes. Medications have been blamed for playing also a pivotal role in the ED occurrence and, particularly, the ß -blockers. Remarkably, the underlying mechanisms have not been fully identified. All the available scientific literature dealing with this topic derives from studies not addressing this issue in HF, but in other settings, (e.g., arterial hypertension) and are also characterized by important methodological flaws. Thus, given the solid evidences arguing in favor of ß -blockers in HF in terms of morbidity, mortality and quality of life, ß -blockers at the maximal tolerated dosage in this patients' category should be recommended, regardless of ED. However, the ED-related issues should not be neglected, and adequate psychological counseling and management should be provided, pursuing the correction of risk factors, the choice of more suitable medications and, in selected cases, adopting specific drugs or devices. The purpose of this narrative review is to highlight the close relationship between ED and HF and, specifically, to focus on a possible ß -blockers' role in determining or, at least, worsening this condition.

Short-period temporal repolarization dispersion in subjects with atrial fibrillation and decompensated heart failure.

BACKGROUND/OBJECTIVES: The association between chronic heart failure (CHF) and permanent atrial fibrillation is very frequent. The repolarization duration was already found predictive for atrial fibrillation. Aim of this study was to evaluate the influence of atrial fibrillation on short period repolarization variables in decompensated CHF patients. METHOD: We used 5 min ECG recordings to assess the mean, standard deviation (SD), and normalized variance (NV) of the following variables: QT end (QTe), QT peak (QTp), and T peak to T end (Te) in 121 decompensated CHF, of whom 40 had permanent atrial fibrillation, too. We reported also the 30-day mortality. RESULTS: QTpSD (p < .01), TeSD (p < .01), QTpVN (p < .01), and TeVN (p < .01) were higher in the atrial fibrillation than among sinus rhythm CHF subjects. Multivariable logistic analysis selected only TeSD (odd ratio, o.r.: 1.32, 95% confidence interval, c.i.: 1.06-1.65, p: .015) associated with atrial fibrillation. A total of 27 patients died during the 30-days follow-up (overall mortality rate 22%), 7 (18%), and 20 (25%) respectively in the atrial fibrillation and sinus rhythm patients. Furthermore, the following variables were associated to the morality risk: NT-pro Brain Natriuretic Peptide (o.r.: 1.00, 95% c.i.: 1.00-1.00, p: .041), left ventricular end diastolic diameter (o.r.: 0.81, 95% c.i.: 0.67-0.96, p: .010), and Te mean (o.r.: 1.04, 95% c.i.: 1.02-1.09, p: .012). CONCLUSION: In decompensated CHF subjects, Te mean seems be associated to mortality and TeSD to the permanent atrial fibrillation. We could hypothesize that, during severe CHF, the multi-level ionic CHF channel derangement could be critical in influencing these non-invasive markers. (ClinicalTrials.gov number, NCT04127162).

Cardiovascular Death Risk in Recovered Mid-Range Ejection Fraction Heart Failure: Insights From Cardiopulmonary Exercise Test.

BACKGROUND: Heart failure with midrange ejection fraction (HFmrEF) represents a heterogeneous category where phenotype, as well as prognostic assessment, remains debated. The present study explores a specific HFmrEF subset, namely those who recovered from a reduced EF (rec-HFmrEF) and, particularly, it focuses on the possible additive prognostic role of cardiopulmonary exercise testing. METHODS AND RESULTS: We analyzed data from 4535 patients with HFrEF and 1176 patients with rec-HFmrEF from the Metabolic Exercise combined with Cardiac and Kidney Indexes database. The end point was cardiovascular death at 5 years. The median follow-up was 1343 days (25th-75th range 627-2403 days). Cardiovascular death occurred in 552 HFrEF and 61 rec-HFmrEF patients. The multivariate analysis confirmed an independent role of the MECKI score's variables in HFrEF (C-index = 0.744) whereas, in the rec-HFmrEF group, only age and peak oxygen uptake (pVO2) remained associated to the end point (C-index = 0.745). A peak oxygen uptake of ≤55% of predicted and a ventilatory efficiency of ≥31 resulted as the most accurate cut-off values in the outcome prediction. CONCLUSIONS: Present data support the cardiopulmonary exercise test and, particularly, the peak oxygen uptake, as a useful tool in the rec-HFmrEF prognostic assessment. A peak VO2 of ≤55% predicted and ventilatory efficiency of ≥31 might help to identify a high-risk rec-HFmrEF subgroup.

Choosing among ß-blockers in heart failure patients according to ß-receptors' location and functions in the cardiopulmonary system.

Several large clinical trials showed a favorable effect of ß-blocker treatment in patients with chronic heart failure (HF) as regards overall mortality, cardiovascular mortality, and hospitalizations. Indeed, the use of ß-blockers is strongly recommended by current international guidelines, and it remains a cornerstone in the pharmacological treatment of HF. Although different types of ß-blockers are currently approved for HF therapy, possible criteria to choose the best ß-blocking agent according to HF patients' characteristics and to ß-receptors' location and functions in the cardiopulmonary system are still lacking. In such a context, a growing body of literature shows remarkable differences between ß-blocker types (ß1-selective blockers versus ß1-ß2 blockers) with respect to alveolar-capillary gas diffusion and chemoreceptor response in HF patients, both factors able to impact on quality of life and, most likely, on prognosis. This review suggests an original algorithm for choosing among the currently available ß-blocking agents based on the knowledge of cardiopulmonary pathophysiology. Particularly, starting from lung physiology and from some experimental models, it focuses on the mechanisms underlying lung mechanics, chemoreceptors, and alveolar-capillary unit impairment in HF. This paper also remarks the significant benefit deriving from the correct use of the different ß-blockers in HF patients through a brief overview of the most important clinical trials.

Time- and frequency-domain analysis of repolarization phase during recovery from exercise in healthy subjects.

BACKGROUND/AIM: Recently, data from temporal dispersion of myocardial repolarization analysis have gained a capital role in the sudden cardiac death risk stratification. Aim of this study was to evaluate the influence of heart rate, autonomic nervous system, and controlled breathing on different myocardial repolarization markers in healthy subjects. METHOD: Myocardial repolarization dispersion markers from short-period (5 minutes) electrocardiogram (ECG) analysis (time and frequency domain) have been obtained in 21 healthy volunteers during the following conditions: free breathing (rest); controlled breathing (resp); the first 5 minutes of postexercise recovery phases (exercisePeak ), maximum sympathetic activation; and during the second 5 minutes of postexercise recovery phases (exerciseRecovery ), intermediate sympathetic activation. Finally, we analyzed the whole repolarization (QTe), the QT peak (QTp), and T peak - T end intervals (Te). RESULTS: During the exercisePeak , major part of repolarization variables changed in comparison to the rest and resp conditions. Particularly, QTe, QTp, and Te standard deviations (QTeSD , QTpSD , and TeSD ); variability indexes (QTeVI and QTpVI), normalized variances (QTeVN, QTpVN, and TeVN); and the ratio between short-term QTe, QTp, and Te variability RR (STVQTe/RR , STVQTp/RR, and STVTe/RR ) increased. During exerciseRecovery , QTpSD (P < .05), QTpVI (P < .05), QTeVN (P < .05), QTpVN (P < .001), TeVN (P < .05), STVQTe/RR (P < .05), STVQTp/RR (P < .001), and STVTe/RR (P < .001) were significantly higher in comparison to the rest. The slope between QTe (0.24 ± 0.06) or QTp (0.17 ± 0.06) and RR were significantly higher than Te (0.07 ± 0.06, P < .001). CONCLUSION: Heart rate and sympathetic activity, obtained during exercise, seem able to influence the time domain markers of myocardial repolarization dispersion in healthy subjects, whereas they do not alter any spectral components.

Hospital mortality in decompensated heart failure. A pilot study.

BACKGROUND/AIM: Heart failure is a leading cause of morbidity and mortality worldwide and it is a major cause of emergency department access for cardiovascular disease patients. Aim of this study was to identify the electrocardiographic (ECG) markers, based on short-term temporal repolarization dispersion, capable to individuate decompensated chronic heart failure (CHF) patients at high mortality risk. METHODS: We obtained the following variables from an ECG recording, monitored via mobile phone, during 5-minute recordings in decompensated CHF patients: RR, QT end (QTe), QT peak (QTp) and T peak to T end (Te) and we calculated mean, standard deviation (SD) and normalized index (N). RESULTS: In-hospital mortality occurred for 25 subjects on 101 studied (25%). Deceased patients showed higher QTeSD (p < 0.01), Te mean (p < 0.01), TeSD (p < 0.05), QTeVN (p < 0.05) than the surviving group. Logistic multivariable analysis evidenced that Te mean was a significant predictor of in-hospital mortality (odd ratio: 0.09, 95% confidence limit: 0.02-0.35, p: 0.001). At multiple regression analysis, TeSD was significantly and positively related only to the NT-pro BNP levels (r: 0.540; p < 0.001). The Te mean (AUC: 0.677 p < 0.01) and TeSD (AUC: 0.647, p: 0.05) showed significant sensitivity/specificity for the event. CONCLUSIONS: The Te mean and TeSD seem to be a promising noninvasive clinical marker able to identify patients with decompensated CHF at high risk of in-hospital mortality.

Age, gender and drug therapy influences on Tpeak-tend interval and on electrical risk score.

BACKGROUND AND OBJECTIVES: Electrical risk score (ERS) has been proposed as easy, inexpensive test to stratify of sudden cardiac death (SCD) risk in subjects with normal left ventricular function. Potentially, aging, gender and drugs can influence ERS affecting two on six electrical markers, particularly, those based on the repolarization. Aim of this study was to establish aging, gender and drug therapy possible influences on ERS and mortality in elderly patients. METHOD: 237 consecutive, low SCD risk-outpatients with asymptomatic and treated cardiovascular risk factors were analyzed. Six simple ECG markers composed ERS: heart rate (>75 bpm); left ventricular hypertrophy (Sokolow-Lyon criteria); delayed QRS transition zone (≥V4), frontal QRS-T angle (>90°), long QTBazett; long T peak to T end interval (Tp-e). We obtained ERS in 237 outpatients, grouped according age (<40 ys, ≥40 to <60 ys and ≥60 ys), gender and drug therapy with or without possible influence on the repolarization phase. RESULTS: Two-hundred-thirty-seven patients were grouped respectively in the following age classes: <40 years old; ≥40 to <60 years old and ≥60 years old. ERS (p < 0.05), QTBazett (p < 0.001), Tp-e (p < 0.001) were higher in older subjects independently from gender, drug therapy and cardiovascular comorbidity. After two years we reported a 7.3% of mortality in the older groups; age (deceased versus survivors: 80 ± 4 versus 73 ± 7 years, p < 0.05) and Tp-e (deceased versus survivors: 117 ± 15 versus 93 ± 21 ms, p < 0.05) were significantly lower in survivors, multivariable logistic regression analysis selected only the Tp-e as significant risk factor for total mortality (odd ratio 1.06, 95% CI: 1.01-1.12, p < 0.05). CONCLUSION: Aging was associated to the ERS and repolarization phase derangement. Tp-e should be considered a marker of total mortality rather than SCD in the over sixty years old patients.

SARS-CoV-2 spread in Northern Italy: what about the pollution role?

The recent epidemic of the new SARS-CoV-2 in the northern regions of Italy is putting the organization of the Italian health system under serious attack. The current emergency requires all possible efforts to stem the spread of the virus. In this context, it is clear that we have the urgent need to rely upon etiopathogenetic data, in order to do all possible efforts to block the epidemic. However, observing the trend of the infections in China and the geographic areas of the main outbreaks, it could be hypothesized that air pollution plays a role. In particular, it has been previously demonstrated, in specific populations, a role of particulate matter in worsening clinical presentation of virus infection in airways. Without prejudice to the ascertained virus spread by air droplets or contaminated surfaces, the factors that could have favored its spread remain to be investigated. Moreover, if these observations were to be confirmed, when the health emergency is resolved, it will be mandatory to redesign an economic-productive model in balance with the environment.

Anemia and Iron Deficiency in Heart Failure: Clinical and Prognostic Role.

Anemia and iron deficiency (ID) represent 2 prevalent, often interrelated, comorbidities in heart failure (HF). Both of them are significantly related to functional capacity and are undoubted predictors of poor prognosis in patients with HF. Although anemia and ID both have "global" detrimental effects, these 2 conditions are too often overlooked in cardiology daily clinical practice. The present review sought to summarize briefly the prevalence and the underlying pathophysiologic mechanisms of anemia and ID as regards HF severity (ie, exercise capacity) and prognosis.

Heart Failure Progression in Hypertrophic Cardiomyopathy　- Possible Insights From Cardiopulmonary Exercise Testing.

BACKGROUND: Heart failure (HF) progression and its complications represent major emergent concerns in hypertrophic cardiomyopathy (HCM). We investigated the possible adjunctive role of cardiopulmonary exercise testing (CPET) in predicting HF-related events. An exercise-derived risk model, theHYPertrophicExercise-derivedRiskHF(HYPERHF), has been developed. METHODS AND RESULTS: A multicenter cohort of 620 consecutive HCM outpatients was recruited and followed (2007 to 2015). The endpoint was death from HF, cardiac transplantation, NYHA III-IV class progression, severe functional deterioration leading to hospitalization for septal reduction, and hospitalization for HF worsening. During a median follow-up of 3.8 years (25-75th centile: 2.3-5.3 years), 84 patients reached the endpoint. Peak circulatory power (peak oxygen consumption * peak systolic blood pressure), ventilatory efficiency and left atrial diameter were independently associated with the endpoint and, accordingly, integrated into the HYPERHFmodel (C index: 0.849; best cutoff value equal to 15%). CONCLUSIONS: CPET is useful in the evaluation of HCM patients. In this context, the HYPERHFscore might allow early identification of those patients at high risk of HF progression and its complications. (Circ J 2016; 80: 2204-2211).

ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism.

PURPOSE: The benefit of angiotensin converting enzyme (ACE) inhibition in chronic heart failure (HF) is partially due to its effects on pulmonary function and particularly on lung diffusion, the latter being counteracted by acetylsalicylic acid (ASA). Tissue ACE activity is largely determined by an insertion/deletion (I/D) polymorphism resulting in three possible genotypes (DD, ID and II). It is not clear if ACE inhibitor therapy could exert different effects in these genotypes. The aim of the study was to understand whether I/D polymorphism interferes with ACE inhibitor's protection of the lungs in HF during acute fluid overload. METHODS: 100 HF patients (left ventricular ejection fraction ≤40 %) in stable clinical conditions, treated with enalapril but without ASA performed pulmonary function tests including lung diffusion (DLco) and its subcomponents, membrane diffusion (Dm) and capillary volume (Vcap), and a cardiopulmonary exercise test before and immediately after rapid infusion of 500 cc saline. RESULTS: ACE I/D genotype prevalence was: DD = 28, ID =55 and II = 17 cases. No significant differences in major pulmonary function and exercise parameters were observed before saline infusion among ACE genotypes. After fluid challenge, DD patients presented a higher DLco and Dm reduction than ID and II (DLco -2.3 ± 1.3 vs. -0.8 ± 1.9 and -0.6 ± 1 mL/mmHg/min, p < 0.0001 and p < 0.01; Dm -7 ± 5 vs. -3.2 ± 7.4 and -1.3 ± 5 mL/mmHg/min, p < 0.05, respectively) and a higher increase in VE/VCO2 slope than II (1.8 ± 1.9 vs. -0.8 ± 2.3, p = 0.01). CONCLUSIONS: ACE DD genotype is associated with higher vulnerability of the alveolar-capillary membrane to acute fluid overload in HF patients treated with ACE inhibitors.

Exercise Performance Is a Prognostic Indicator in Elderly Patients With Chronic Heart Failure--Application of Metabolic Exercise Cardiac Kidney Indexes Score.

BACKGROUND: In patients with chronic heart failure (HF) the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score, is a predictor of cardiovascular death and urgent heart transplantation. We investigated the relationship between age, exercise tolerance and the prognostic value of the MECKI score. METHODS AND RESULTS: We analyzed data from 3,794 patients with chronic systolic HF. The primary endpoint was a composite of cardiovascular death and urgent heart transplantation. Older patients had higher prevalence of comorbidities and lower exercise performance compared with younger subjects (peak V̇O2, 925 vs. 1,351 L/min; P<0.0001; V̇E/V̇CO2slope, 33.2 vs. 28.3; P>0.0001). The rate of the primary endpoint was 19% in the highest age quartile and 14% in the lowest quartile. At multivariable analysis, the independent predictors of the primary endpoint were left ventricular ejection fraction (LVEF), eGFR, peak V̇O2, serum Na(+)and the use of ß-blockers in patients aged ≥70 years, and LVEF, eGFR and peak V̇O2in younger subjects. The MECKI risk score increased across age subgroups, but on receiver operating characteristic curve analysis its prognostic power was similar in both patients aged ≥70 and <70 years. CONCLUSIONS: Older patients with HF are a high-risk population with lower exercise performance. The MECKI score increased according to age and maintained its prognostic value also in older patients.

Renal function and peak exercise oxygen consumption in chronic heart failure with reduced left ventricular ejection fraction.

BACKGROUND: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS: Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

Spatial QT Dispersion Predicts Nonsustained Ventricular Tachycardia and Correlates with Confined Systodiastolic Dysfunction in Hypertrophic Cardiomyopathy.

OBJECTIVES: An increased dispersion of myocardial repolarization represents one of the mechanisms underlying the arrhythmic risk in hypertrophic cardiomyopathy (HCM). We investigated spatial myocardial repolarization dispersion indices in HCM patients with nonsustained ventricular tachycardia (NSVT) and, contextually, their main clinical determinants. METHODS: Fifty-two well-matched HCM outpatients were categorized into two groups according to the presence or the absence of NSVT at 24-hour Holter electrocardiogram (ECG) monitoring. Each patient underwent a clinical examination, including Doppler echocardiogram integrated with tissue Doppler imaging, cardiac magnetic resonance, and 12-lead surface ECG to calculate the dispersion for the following intervals: QRS, Q-Tend (QTe), Q-Tpeak, Tpeak-Tend (TpTe), J-Tpeak, and J-Tend. RESULTS: The NSVT group showed only QTe dispersion and TpTe dispersion values to be significantly higher than their counterparts. NSVT occurrence was independently predicted by late gadolinium enhancement presence (p=0.021) and QTe Bazett dispersion (p=0.030), the latter strongly associated with the myocardial performance index (MPI) obtained at the basal segment of the interventricular septum (p=0.0004). CONCLUSION: Our data support QTe dispersion as an easy and noninvasive tool for identifying HCM patients with NSVT propensity. The strong relationship between QTe dispersion and MPI allows us to hypothesize an intriguing link between electrical instability and confined myocardial areas of systodiastolic dysfunction.

Myocardial repolarization dispersion and late gadolinium enhancement in patients with hypertrophic cardiomyopathy.

BACKGROUND: Growing evidence suggests that late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) is an additive marker of disease severity, and possibly of arrhythmic risk, in hypertrophic cardiomyopathy (HCM). We investigated the possible relationship between LGE and markers of myocardial repolarization dispersion in HCM. METHODS AND RESULTS: Eighty-five HCM outpatients underwent CMR and short-period electrocardiogram analysis to calculate the temporal myocardial repolarization dispersion through the QT variance normalized for QT mean (QTVN) and the QT variability index (QTVI). The QT dispersion in the spatial domain was also obtained. Patients with LGE (62%) had higher left atrial volume, maximum wall thickness, and left ventricular mass (P<0.0001), as well as a greater prevalence of non-sustained ventricular tachycardia (P<0.0001) and hypotensive blood pressure response (P=0.044). Both QTVN and QTVI were higher in the group with LGE (P<0.0001). At multivariate analysis, using QTVI as the dependent variable, %LGE (P<0.0001), age (P<0.0001), left ventricular outflow obstruction (P=0.038), and sudden cardiac death risk factor burden (P=0.020) reached statistical significance. Otherwise, only %LGE (P=0.005) and left ventricular mass index (P=0.015) remained associated with QTVN. CONCLUSIONS: Temporal myocardial repolarization dispersion correlates with LGE extent. Whether these variables could be useful in HCM clinical management warrants confirmation by larger prospective studies.

[QT Variability Index as a tool for risk stratification of sudden cardiac death]. / Il QT Variability Index come strumento per la stratificazione del rischio di morte improvvisa.

Sudden cardiac death is the leading cause of mortality in patients with chronic heart failure (CHF) and history of myocardial infarction. Selection of patients at risk of sudden cardiac death is dramatically important to choose the correct therapeutic approach. The QT Variability Index (QTVI) is a non-invasive measure of repolarization lability that has been applied to a wide variety of subjects with cardiovascular disease. It is a ratio of normalized QT variability to normalized heart rate variability, and therefore includes an assessment of the autonomic nervous system tone. As opposed to T wave alternans, QTVI assesses variance in repolarization at all frequencies. Recent studies suggest that QTVI may help clinicians choosing the appropriate implantable cardiovester defibrillator timing implantation, in patients with dilated or hypertrophic cardiomyopathy or CHF because of its efficacy in patient evaluation and follow-up.