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1.
The conundrum of patients with obesity, exercise intolerance, elevated ventricular filling pressures and a measured ejection fraction in the normal range.
Packer, M
European journal of heart failure. 2019;(2):156-162
Abstract
Patients with obesity, a reduced exercise capacity, increased cardiac filling pressures and a measured left ventricular ejection fraction in the normal range do not have a homogeneous disorder, but instead, exhibit one of three phenotypes. First, many obese people exhibit sodium retention, plasma volume expansion and cardiac enlargement, and some are likely to have heart failure that is related to hypervolaemia, even though cardiac index and circulating levels of natriuretic peptides are not meaningfully increased. Second, in some middle-aged men and women (particularly those with minimal co-morbidities), levels of natriuretic peptides increase markedly and can lower systemic vascular resistance, thus leading to high-output heart failure (HOHF) and glomerular hyperfiltration. Third, older obese people, particularly women with multiple co-morbidities, exhibit the syndrome of heart failure with a preserved ejection fraction (HFpEF). Despite degrees of plasma volume expansion similar to HOHF, these patients exhibit only modestly increased ventricular dimensions and circulating levels of natriuretic peptides (despite a high prevalence of atrial fibrillation), and glomerular function is characteristically impaired. A conceptual framework is proposed to distinguish among the three phenotypes seen in obese patients with exercise intolerance, increased ventricular filling pressures and a measured left ventricular ejection fraction in the normal range, since they may respond differently to therapeutic interventions. Efforts are needed to enhance the recognition of heart failure in obese people and to ensure that clinical trials that are designed to study patients with HFpEF actually enrol those who have the disease.
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2.
The effects of sodium-glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions.
Lan, NSR, Fegan, PG, Yeap, BB, Dwivedi, G
ESC heart failure. 2019;(5):927-935
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a unique class of oral anti-hyperglycaemic medications that act to reduce glucose reabsorption in the renal proximal tubules, thereby enhancing urinary glucose excretion. Large randomized placebo-controlled trials in people with diabetes at high cardiovascular risk have demonstrated that SGLT2 inhibitors reduce heart failure hospitalization within months of commencing therapy. These findings are of considerable interest, as diabetes is associated with an increased risk of both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. In addition, left ventricular (LV) hypertrophy and impaired diastolic function is thought to be more prevalent in people with diabetes. Although many hypotheses have been proposed, the underlying mechanisms through which SGLT2 inhibitors reduce the risk of heart failure in people with diabetes are not fully understood. Given the rapid reduction in heart failure hospitalization, it is conceivable that the benefits of SGLT2 inhibitors are due to favourable haemodynamic and metabolic effects on LV function. Several clinical studies have been conducted to investigate the effect of SGLT2 inhibitors on LV structure and function and have found that LV mass index and diastolic function improve following SGLT2 inhibitor therapy in people with type 2 diabetes. If these findings are confirmed in future studies utilizing novel cardiac imaging modalities and large randomized controlled trials, then this will bring new hope for the prevention and management of heart failure with preserved ejection fraction, for which no current treatments have been shown to reduce mortality. At the present time, SGLT2 inhibitors are indicated for the treatment of type 2 diabetes; however, the results of ongoing trials in participants with heart failure but without diabetes are eagerly awaited. The purpose of this review is to summarize current knowledge regarding the effects of SGLT2 inhibitors on LV function, particularly the findings from clinical studies, proposed biological mechanisms, and future directions.
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3.
Cardiac contractility modulation: mechanisms of action in heart failure with reduced ejection fraction and beyond.
Tschöpe, C, Kherad, B, Klein, O, Lipp, A, Blaschke, F, Gutterman, D, Burkhoff, D, Hamdani, N, Spillmann, F, Van Linthout, S
European journal of heart failure. 2019;(1):14-22
Abstract
Heart failure (HF) is responsible for substantial morbidity and mortality and is increasing in prevalence. Although there has been remarkable progress in the treatment of HF with reduced ejection fraction (HFrEF), morbidity and mortality are still substantial. Cardiac contractility modulation (CCM) signals, consisting of biphasic high-voltage bipolar signals delivered to the right ventricular septum during the absolute refractory period, have been shown to improve symptoms, exercise tolerance and quality of life and reduce the rate of HF hospitalizations in patients with ejection fractions (EF) between 25% and 45%. CCM therapy is currently approved in the European Union, China, India, Australia and Brazil for use in symptomatic HFrEF patients with normal or slightly prolonged QRS duration. CCM is particularly beneficial in patients with baseline EF between 35% and 45%, which includes half the range of HF patients with mid-range EFs (HFmrEF). At the cellular level, CCM has been shown in HFrEF patients to improve calcium handling, to reverse the foetal myocyte gene programme associated with HF, and to facilitate reverse remodelling. This review highlights the preclinical and clinical literature related to CCM in HFrEF and HFmrEF and outlines the potential of CCM for HF with preserved EF, concluding that CCM may fill an important unmet need in the therapeutic approach to HF across the range of EFs.
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4.
Interrelationship between diabetes mellitus and heart failure: the role of peroxisome proliferator-activated receptors in left ventricle performance.
Oikonomou, E, Mourouzis, K, Fountoulakis, P, Papamikroulis, GA, Siasos, G, Antonopoulos, A, Vogiatzi, G, Tsalamadris, S, Vavuranakis, M, Tousoulis, D
Heart failure reviews. 2018;(3):389-408
Abstract
Heart failure (HF) is a common cardiac syndrome, whose pathophysiology involves complex mechanisms, some of which remain unknown. Diabetes mellitus (DM) constitutes not only a glucose metabolic disorder accompanied by insulin resistance but also a risk factor for cardiovascular disease and HF. During the last years though emerging data set up, a bidirectional interrelationship between these two entities. In the case of DM impaired calcium homeostasis, free fatty acid metabolism, redox state, and advance glycation end products may accelerate cardiac dysfunction. On the other hand, when HF exists, hypoperfusion of the liver and pancreas, b-blocker and diuretic treatment, and autonomic nervous system dysfunction may cause impairment of glucose metabolism. These molecular pathways may be used as therapeutic targets for novel antidiabetic agents. Peroxisome proliferator-activated receptors (PPARs) not only improve insulin resistance and glucose and lipid metabolism but also manifest a diversity of actions directly or indirectly associated with systolic or diastolic performance of left ventricle and symptoms of HF. Interestingly, they may beneficially affect remodeling of the left ventricle, fibrosis, and diastolic performance but they may cause impaired water handing, sodium retention, and decompensation of HF which should be taken into consideration in the management of patients with DM. In this review article, we present the pathophysiological data linking HF with DM and we focus on the molecular mechanisms of PPARs agonists in left ventricle systolic and diastolic performance providing useful insights in the molecular mechanism of this class of metabolically active regiments.
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5.
Vitamin D and new-onset atrial fibrillation: A meta-analysis of randomized controlled trials.
Huang, WL, Yang, J, Yang, J, Wang, HB, Yang, CJ, Yang, Y
Hellenic journal of cardiology : HJC = Hellenike kardiologike epitheorese. 2018;(2):72-77
Abstract
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which affects 1.5% to 2% of the general population. More than six million Europeans suffer from AF. To research vitamin D levels in the prevention of new-onset atrial fibrillation (AF), we conducted a systematic review of randomized controlled trials (RCTs). We focused on the vitamin D levels in the prevention of new-onset AF. The outcomes assessed were vitamin D levels, left ventricular ejection fraction (LVEF), and left atrium diameter. Six RCTs ultimately met the inclusion criteria in the meta-analysis. The outcomes of Vitamin D levels (MD = -4.27, 95% CI = -5.20 to-3.34, P = 0.30) in the new-onset AF showed no significant difference. The left atrium diameter (MD = 1.96, 95% CI = 1.48 to 2.60, P < 0.01) between new-onset AF and LVEF (MD = -0.92, 95% CI = -1.59 to -0.26, P < 0.01) showed significant difference. Our study shows that circulating vitamin D levels may not play a major role in the development of new-onset AF.
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6.
Changes in left ventricular geometry during antihypertensive treatment.
Salvetti, M, Paini, A, Bertacchini, F, Stassaldi, D, Aggiusti, C, Agabiti Rosei, C, Bassetti, D, Agabiti-Rosei, E, Muiesan, ML
Pharmacological research. 2018;:193-199
Abstract
UNLABELLED The reduction of echocardiographic left ventricular (LV) mass and the change toward a less concentric geometry during antihypertensive treatment are independently associated with a better prognosis. Blood pressure-lowering treatment may reduce cardiac hypertrophy, although different effect on changes of LV mass have been reported among antihypertensive drug classes, while changes in echocardiographic evaluated LV geometry have not been systemically evaluated. It is not yet clear whether antihypertensive drugs may influence LV geometry. Our aim was to compare the effects of diuretics (D), beta-blockers (BB), calcium channel blockers (CCB), angiotensin-converting enzyme inhibitors (ACE-I), and angiotensin receptor blockers (ARBS) on relative wall thickness (RWT) in patients with hypertension on the basis of prospective, randomized comparative studies. METHODS MEDLINE, and the ISI Web of Sciences were searched for randomized clinical trials evaluating LV mass and geometry at baseline and end follow-up. We have performed a pooled pairwise comparisons of the effect of the 5 major drug classes on relative wall thickness changes, and of each drug class versus other classes statistically combined. RESULTS We selected 53 publications involving 7684 patients. A significant correlation was observed between percent changes from baseline to end of treatment in LV mass and those in systolic BP (r = 0.44, p < 0.001). Reduction of LV mass was significantly greater with CCB than with BB (P < 0.02) without other significant differences between drug classes. Percent changes in RWT were related to percent changes in LV mass/LVmass index (r = 0.68, p = 0.016) and of SBP (r = 0.64 p < 0.033). RWT decreased during treatment with all classes of drugs, except the combination of BB and D; the decrease of RWT was less with diuretics and sympatholytic drugs. CONCLUSIONS In studies evaluating the effect of different classes of antihypertensive drugs on LV mass, the reduction of relative wall thickness seems to be less during treatment with diuretics.
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7.
Perioperative Management of the Right and Left Ventricles.
Lampert, BC
Cardiology clinics. 2018;(4):495-506
Abstract
Left ventricular assist devices (LVADs) improve survival in select advanced heart failure patients and rates of LVAD implantation are growing. LVAD support carries significant morbidity and mortality with the greatest risk in the perioperative period. Strategies have evolved to minimize this risk. Medical and mechanical support is used for right and left ventricular optimization. Other strategies emphasize improving nutrition, hematologic abnormalities, infection risk, and renal function. Intraoperative approaches highlight anesthesia-related issues, management of concomitant valve disease, right ventricular failure, and weaning from cardiopulmonary bypass. Postoperative efforts concentrate on augmenting right ventricular function, supporting end-organ recovery, and quickly identifying complications.
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8.
The role of arterial hypertension in development heart failure with preserved ejection fraction: just a risk factor or something more?
Tadic, M, Cuspidi, C, Frydas, A, Grassi, G
Heart failure reviews. 2018;(5):631-639
Abstract
Heart failure with preserved ejection fraction (HFpEF) is an entity that still raises many questions. The agreement about definition, pathophysiology, and therapeutic approach is still missing. Arterial hypertension is present in majority of patients with HFpEF, and it is still not clear if it represent a risk factor or "sine qua non" condition for HFpEF development. The underlying mechanisms of hypertension and HFpEF involve the same biohumoral systems: renin-angiotensin-aldosterone, sympathetic nervous system, and oxidative stress. However, not all hypertensive patients have HFpEF. The predisposition of some hypertensive patients to develop HFpEF needs to be resolved. Large randomized controlled trials did not prove the usefulness of renin-angiotensin-aldosterone inhibitors, diuretics, calcium channel blockers, and beta-blockers in HFpEF patients. The majority of studies did not succeed to demonstrate the reduction of cardiovascular and all-cause mortality in HFpEF individuals. One of the major limitations in these investigations was the inconsistency of HFpEF definition, which mainly refers to left ventricular ejection fraction (LVEF) cut-off that ranged from 40 to 50% in different studies. This review article provides the available data about pathophysiology and mechanisms that connect hypertension and HFpEF, investigations and therapy used in both conditions.
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9.
Benefits and Harms of Sacubitril in Adults With Heart Failure and Reduced Left Ventricular Ejection Fraction.
Aronow, WS, Shamliyan, TA
The American journal of cardiology. 2017;(7):1166-1170
Abstract
The quality of evidence regarding patient-centered outcomes in adults with heart failure (HF) after sacubitril combined with valsartan has not been systematically appraised. We searched 4 databases in February 2017 and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach. We reviewed 1 meta-analysis and multiple publications of 2 randomized controlled trials (RCT) and 1 unpublished RCT. In adults with HF and reduced ejection fraction, low-quality evidence from 1 RCT of 8,432 patients suggests that sacubitril combined with valsartan reduces all-cause (number needed to treat [NNT] to prevent 1 event [NNTp] = 35) and cardiovascular mortality (NNTp = 32), hospitalization (NNTp = 11), emergency visits (NNTp = 69), and serious adverse effects, leading to treatment discontinuation (NNTp = 63) and improves quality of life when compared with enalapril. In adults with HF and preserved ejection fraction, very low-quality evidence from 1 RCT of 301 patients suggests that there are no differences in mortality, morbidity, or adverse effects between sacubitril combined with valsartan and valsartan alone. In conclusion, in adults with HF and reduced ejection fraction, to reduce cardiovascular mortality and hospitalizations and improve quality of life, clinicians may recommend sacubitril combined with valsartan over angiotensin-converting enzyme inhibitors.
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10.
Effects of High-Intensity Interval Training on Aerobic Capacity in Cardiac Patients: A Systematic Review with Meta-Analysis.
Xie, B, Yan, X, Cai, X, Li, J
BioMed research international. 2017;:5420840
Abstract
Purpose. The aim of this study was to compare the effects of high-intensity interval training (INTERVAL) and moderate-intensity continuous training (CONTINUOUS) on aerobic capacity in cardiac patients. Methods. A meta-analysis identified by searching the PubMed, Cochrane Library, EMBASE, and Web of Science databases from inception through December 2016 compared the effects of INTERVAL and CONTINUOUS among cardiac patients. Results. Twenty-one studies involving 736 participants with cardiac diseases were included. Compared with CONTINUOUS, INTERVAL was associated with greater improvement in peak VO2 (mean difference 1.76 mL/kg/min, 95% confidence interval 1.06 to 2.46 mL/kg/min, p < 0.001) and VO2 at AT (mean difference 0.90 mL/kg/min, 95% confidence interval 0.0 to 1.72 mL/kg/min, p = 0.03). No significant difference between the INTERVAL and CONTINUOUS groups was observed in terms of peak heart rate, peak minute ventilation, VE/VCO2 slope and respiratory exchange ratio, body mass, systolic or diastolic blood pressure, triglyceride or low- or high-density lipoprotein cholesterol level, flow-mediated dilation, or left ventricular ejection fraction. Conclusions. This study showed that INTERVAL improves aerobic capacity more effectively than does CONTINUOUS in cardiac patients. Further studies with larger samples are needed to confirm our observations.