Understanding the functional limitation in hypertrophic cardiomyopathy, the most common inherited heart disease, is challenging. In addition to the occurrence of disease-related complications, ...several factors are potential determinants of exercise limitation, including left ventricular hypertrophy, myocardial fiber disarray, left ventricular outflow tract obstruction, microvascular ischemia, and interstitial fibrosis. Furthermore, drugs commonly used in the daily management of these patients may interfere with exercise capacity, especially those with a negative chronotropic effect. Cardiopulmonary exercise testing can safely and objectively evaluate the functional capacity of these patients and help the physician in understanding the mechanisms that underlie this limitation. Features that reduce exercise capacity may predict progression to heart failure in these patients and even the risk of sudden cardiac death.
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.
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.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.
Little is known about the impact of air pollution on neuroautonomic system. The authors have investigated possible influence of air pollution and outdoor temperature on the carotid sinus ...hypersensitivity (CSH), as main cause of neurally mediated syncope in forty-years-old subjects and older. Pollutants’ concentrations and outdoor temperature of days in which 179 subjects with recurrent syncope underwent carotid sinus massage (CSM) were analyzed. Before this manoeuvre, cardiovascular control by short period heart and blood pressure spectral duration of segment between the end of P and R ECG-waves (PeR) were registred; RR variability on the same short period ECG recordings and their spectral coherence were also analyzed. CSH was found in 57 patients (28 with cardioinhibitory response and 29 subjects showed vasodepressor reaction), while 122 subjects had a normal response. CSM performed during high ozone concentrations was associated with slightly higher risk of cardioinhibitory response (odd ratio 1.012, 95% CI 1.001–1.023, p < 0.05), but neither this or other polluting agent nor outdoor temperature seemed to influence autonomic control in basal resting condition. Thus, ozone seemed to influence response to the CSM in CSH patients and it is probably able to facilitate a cardioinhibitory response, perhaps through an increase of nerve acetylcholine release. P→PR coherence could be useful in predicting a sinus cardioinhibitory hypersensitivity in those cases when CSM is contraindicated.
In hypertrophic cardiomyopathy (HCM), most of the factors associated with the risk of sudden cardiac death (SCD) are also involved in the pathophysiology of exercise limitation. The present ...multicentre study investigated possible ability of cardiopulmonary exercise test in improving contemporary strategies for SCD risk stratification.
A total of 623 consecutive outpatients with HCM, from five tertiary Italian HCM centres, were recruited and prospectively followed, between September 2007 and April 2015. The study composite end point was SCD, aborted SCD and appropriate implantable cardioverter defibrillator (ICD) interventions.
During a median follow-up of 3.7 years (25th-75th centile: 2.2-5.1 years), 25 patients reached the end point at 5 years (3 SCD, 4 aborted SCD, 18 appropriate ICD interventions). At multivariate analysis, ventilation versus carbon dioxide relation during exercise (VE/VCO2 slope) remains independently associated to the study end point either when challenged with the 2011 American College of Cardiology Foundation/American Heart Association guidelines-derived score (C index 0.748) or with the 2014 European Society of Cardiology guidelines-derived score (C index 0.750). A VE/VCO2 slope cut-off value of 31 showed the best accuracy in predicting the SCD end point within the entire HCM study cohort (sensitivity 64%, specificity 72%, area under the curve 0.72).
Our data suggest that the VE/VCO2 slope might improve SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to contemporary guidelines. There is a need for further larger studies, possibly on independent cohorts, to confirm our preliminary findings.
Heart failure with mid-range ejection fraction represents a heterogeneous and relatively young heart failure category accounting for nearly 20–30% of the overall heart failure population. Due to its ...complex phenotype, a reliable clinical picture of heart failure with mid-range ejection fraction patients as well as a definite risk stratification are still relevant unsolved issues. In such a context, there is growing interest in a comprehensive functional assessment by means of a cardiopulmonary exercise test, yet considered a cornerstone in the clinical management of patients with heart failure and reduced ejection fraction. Indeed, the cardiopulmonary exercise test has also been found to be particularly useful in the heart failure with mid-range ejection fraction category, several cardiopulmonary exercise test-derived parameters being associated with a poor outcome. In particular, a recent contribution by the metabolic exercise combined with cardiac and kidney indexes research group showed an independent association between the peak oxygen uptake and pure cardiovascular mortality in a large cohort of recovered heart failure with mid-range ejection fraction patients. Contextually, the same study supplied an easy approach to identify a high-risk heart failure with mid-range ejection fraction subset by using a combination of peak oxygen uptake and ventilatory efficiency cut-off values, namely 55% of the maximum predicted and 31, respectively. Thus, looking at the above-mentioned promising results and waiting for specific trials, it is reasonable to consider cardiopulmonary exercise test assessment as part of the heart failure with mid-range ejection fraction work-up in order to identify those patients with an unfavourable functional profile who probably deserve a close clinical follow-up and, probably, more aggressive therapeutic strategies.
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.
Cardiac output (Q˙) is a key parameter in the assessment of cardiac function, its measurement being crucial for the diagnosis, treatment, and prognostic evaluation of all heart diseases. Until ...recently, Q˙ determination at peak exercise has been possible through invasive methods, so that normal values were obtained in studies based on small populations.
Nowadays, peak Q˙ can be measured noninvasively by means of the inert gas rebreathing (IGR) technique. The present study was undertaken to provide reference values for peak Q˙ in the normal general population and to obtain a formula able to estimate peak exercise Q˙ from measured peak oxygen uptake (V˙o2).
We studied 500 normal subjects (age, 44.9 ± 1.5 years; range, 18-77 years; 260 men, 240 women) who underwent a maximal cardiopulmonary exercise test with peak Q˙ measurement by IGR. In the overall study sample, peak Q˙ was 13.2 ± 3.5 L/min (men, 15.3 ± 3.3 L/min; women, 11.0 ± 2.0 L/min; P < .001) and peak V˙o2 was 95% ± 18% of the maximum predicted value (men, 95% ± 19%; women, 95% ± 18%). Peak V˙o2 and peak Q˙ progressively decreased with age (R2, 0.082; P < .001; and R2, 0.144; P < .001, respectively). The V˙o2-derived formula to measure Q˙ at peak exercise was (4.4 × peak V˙o2) + 4.3 in the overall study cohort, (4.3 × peak V˙o2) + 4.5 in men, and (4.9 × peak V˙o2) + 3.6 in women.
The simultaneous measurement of Q˙ and V˙o2 at peak exercise in a large sample of healthy subjects provided an equation to predict peak Q˙ from peak V˙o2 values.
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