Effects of exercise training in heart failure with preserved ejection fraction: an updated systematic literature review.

Physical activity is associated with a lower risk of adverse cardiovascular outcomes, including heart failure (HF). Exercise training is a class IA level recommendation in patients with stable HF, but its impact is less clear in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to analyze the effects of the exercise training on cardiovascular outcomes in patients with HFpEF. A systematic literature search was conducted on the main electronic databases, proceedings of major meetings, and reference lists of the identified studies, using specific terms for only English language studies published between 2000 and 2018. We followed the PRISMA to perform our review. Quality of studies was also assessed. The systematic review identified 9 studies on 348 patients, of moderate (n = 2) to good (n = 7) quality. The training consisted of a combination of supervised in-hospital and home-based outpatient programs, including aerobic exercise, endurance and resistance training, walking, and treadmill and bicycle ergometer. Most of the protocols ranged 12-16 weeks, with a frequency of 2-3 sessions weekly, lasting 20-60 min per session. There were significant improvements in peak oxygen uptake, 6-min walking test distance, and ventilatory threshold, whereas quality of life and echocardiographic parameters improved only in some studies. Endothelial function/arterial stiffness remained unchanged. No adverse events were reported. Appropriate exercise programs are able to get a favorable cardiovascular outcome in patients with HFpEF. This could also benefit in terms of quality of life, even if more controversial. Further researches are necessary.

Clinical significance and prognostic value of right bundle branch block in permanent pacemaker patients.

AIMS: In patients undergoing pacemaker implantation with no prior history of heart failure (HF), the presence of left bundle branch block (LBBB) has been identified as an independent predictor of HF-related death or hospitalization, while the prognostic significance of right bundle branch block (RBBB) remains uncertain. We aimed to assess the long-term risk of all-cause mortality in patients with a standard indication for permanent pacing and normal or moderately depressed left ventricular function when RBBB is detected at the time of implantation. METHODS: We retrospectively enrolled 1348 consecutive patients who had undergone single- or dual-chamber pacemaker implantation at the study center, from January 1990 to December 2022. Patients with a left ventricular ejection fraction ≤35% or a prior diagnosis of HF were excluded. RESULTS: The baseline 12-lead electrocardiogram revealed an RBBB in 241 (18%) and an LBBB in 98 (7%) patients. During a median follow-up of 65 [25th-75th percentile: 32-117] months, 704 (52%) patients died. The combined endpoint of cardiovascular death or HF hospitalization was reached by 173 (13%) patients. On multivariate analysis, RBBB was confirmed as an independent predictor of death [hazard ratio, 1.33; 95% confidence interval (CI), 1.09-1.63; P  = 0.005]. However, when considering the combined endpoint of cardiovascular death and HF hospitalization, this endpoint was independently associated with LBBB (hazard ratio, 2.13; 95% CI, 1.38-3.29; P  < 0.001), but not with RBBB. CONCLUSION: In patients with standard pacemaker indications and normal or moderately depressed left ventricular function, the presence of basal RBBB was an independent predictor of mortality. However, it was not associated with the combined endpoint of cardiovascular death and HF hospitalization.

Incidence and predictors of heart failure hospitalization and death in permanent pacemaker patients: a single-centre experience over medium-term follow-up.

AIM: The aim of this study was to assess the incidence and clinical predictors of the development of new-onset heart failure (HF) over medium-term follow-up, in patients treated with permanent pacing in daily clinical practice. METHODS AND RESULTS: We retrospectively enrolled all consecutive patients who underwent single- or dual-chamber pacemaker implantation at the study centre. Patients with a left ventricular ejection fraction (LVEF) ≤35% or a prior diagnosis of HF were excluded. Ventricular leads were routinely implanted in the right apex. Pacemakers were implanted in 490 patients with a standard pacemaker indication and LVEF >35%. Left bundle-branch block (LBBB) was reported in 30 (8%) patients, and an LVEF <50% in 64 (13%) patients. During a follow-up of 27 ± 21 months, 32 (7%) patients reached the combined endpoint of HF death or hospitalization. On multivariate analysis, LBBB (HR, 3.50; 95% CI, 1.1-11.1; P = 0.033) and LVEF <50% (HR, 5.1; 95% CI, 1.9-14.2; P = 0.002) were confirmed as independent predictors of HF death or hospitalization. Patients with LVEF <50% and/or LBBB displayed significantly higher rates of HF death or hospitalization (log-rank test, all P<0.001). CONCLUSION: The majority of patients with a standard indication for permanent pacing and normal LV function remained in a clinically stable condition after pacemaker implantation. However, ∼7% of patients developed new-onset HF over a period of follow-up of 27 months, and the presence of LBBB and LVEF <50% at the baseline predicted HF death or hospitalization.

Non-high-density lipoprotein cholesterol versus low-density lipoprotein cholesterol in clinical practice: ANMCO position paper.

Bloodstream cholesterol is a central contributor to atherosclerotic cardiovascular diseases. For several decades, low-density lipoprotein cholesterol (LDL-C) has been the main biomarker for the prediction of cardiovascular events and therapeutic target of lipid-lowering treatments. More recently, several findings have supported the greater reliability of non-high-density lipoprotein cholesterol (non-HDL-C) as a predictive factor and possible therapeutic target in refining antiatherogenic treatments, especially among patients with lower LDL-C and higher triglyceride values. This article discusses the limits of current standard methods for assessing LDL-C levels and emphasizes the persistent residual cardiovascular risk in patients treated with lipid-lowering agents on the basis of recommended LDL-C targets. It highlights that patients with controlled LDL-C and non-targeted non-HDL-C have a higher cardiovascular risk. The article focuses on the role of non-HDL-C as a better predictor of atherosclerotic disease as compared with LDL-C and as a therapeutic target. Finally, this article includes an executive summary aimed at refining preventive approaches in atherosclerotic cardiovascular disease.

Continuous monitoring of sleep-disordered breathing with pacemakers: Indexes for risk stratification of atrial fibrillation and risk of stroke.

BACKGROUND: Sleep apnea (SA) is a risk factor for atrial fibrillation (AF). Advanced pacemakers are now able to calculate indexes of SA severity. HYPOTHESIS: We investigated the changes in pacemaker-measured indexes of SA, we assessed their predictive value for AF occurrence and the associated risk of stroke and death at long-term. METHODS: We enrolled 439 recipients of a pacemaker endowed with an algorithm for the calculation of a Respiratory Disturbance Index (RDI). The RDI variability was measured over the first 12 months after implantation, as well as its potential association with the occurrence of AF, defined as device-detected cumulative AF burden ≥6 hoursours in a day. RESULTS: The individual RDI mean was 30 ± 18 episodes/h, and the RDI maximum was 59 ± 21 episodes/h. RDI ≥30 episodes/h was detected in 351 (80%) patients during at least one night. The proportion of nights with RDI ≥30 episodes/h was 14% (2%-36%). AF ≥6 hours was detected in 129 (29%) patients during the first 12 months. The risk of AF was higher in patients with RDI maximum ≥63 episodes/h (HR:1.74; 95%CI: 1.22-2.48; P = .001) and with RDI mean ≥ 46 episodes/h (HR:1.63; 95%CI: 1.03-2.57; P = .014). The risk of all-cause death or stroke was higher in patients with AF burden ≥6 hours (HR:1.75; 95%CI: 1.06-2.86; P = .016). Moreover, among patients with no previous history of AF the risk was higher in those with RDI maximum ≥63 episodes/h (HR:1.96; 95%CI: 1.06-3.63; P = .031). CONCLUSIONS: Pacemaker-detected SA showed a considerable variability during follow-up. We confirmed the association between RDI and higher risk of AF, and we observed an association between higher RDI maximum and all-cause death or stroke among patients with no previous history of AF.

Cardiac Rehabilitation and Endothelial Function.

Endothelial dysfunction is an early abnormality in the process of atherosclerosis and cardiovascular disease and has been associated with worse clinical outcome. Cardiac rehabilitation (CR) has been reported to be helpful to reduce cardiovascular events in various types of cardiac disease, but the mechanisms of its beneficial effects remain only partially known. In this article, we review the studies that assessed the effect of CR on endothelial function in patients with various cardiac conditions. Available data show that CR significantly improves impaired endothelial function in these patients, which may contribute to the beneficial effects of CR on clinical outcome.

Baseline apnoea/hypopnoea index and high-sensitivity C-reactive protein for the risk of recurrence of atrial fibrillation after successful electrical cardioversion: a predictive model based upon the multiple effects of significant variables.

AIMS: We tested apnoea/hypopnoea index (AHI), high-sensitivity (hs) C-reactive protein and clinical/instrumental variables as predictors of atrial fibrillation (AF) recurrence over 1-year follow-up after successful electrical cardioversion. METHODS AND RESULTS: We enrolled 158 consecutive patients. Apnoea/hypopnoea index was assessed with standard overnight polysomnography and hs-C-reactive protein with immunonephelometry assay the day before electrical cardioversion. Atrial fibrillation recurrences occurred in 81 patients (51%). Predictors at univariate analysis were: AHI > or = 15 events/h (P = 0.001), hs-C-reactive protein >0.30 mg/dL (P = 0.009), AF duration >3 days (P = 0.008), diabetes (P = 0.03), and ongoing anti-arrhythmic therapy at the time of electrical cardioversion (P = 0.03). Survival analysis confirmed that patients with AHI > or = 15 events/h and hs-C-reactive protein > 0.30 mg/dL had a higher recurrence rate of AF (log rank P = 0.0006 and P = 0.01, respectively). Predictors at multivariate analysis were: AHI > or = 15 events/h (P = 0.003), hs-C-reactive protein > 0.30 mg/dL (P = 0.01) and ongoing anti-arrhythmic therapy (P = 0.04). A predictive model based upon the multiple effects of significant variables plus age as a continuous variable stratified the risk of AF recurrence, more than tripled with all dichotomized variables altered with respect to normal variables (85 vs. 27%). CONCLUSION: AHI > or = 15 events/h and hs-C-reactive protein > 0.30 mg/dL are the strongest predictors of the predictors chosen of AF recurrence after successful electrical cardioversion over 1-year follow-up.

Fixed and Low-Dose Combinations of Blood Pressure-Lowering Agents: For the Many or the Few?

Despite the widespread availability of several effective classes of drugs, systemic arterial hypertension remains poorly controlled in the majority of patients worldwide. In this article, we discuss the different modalities and effects of combination therapy and possible future research questions. Treatment with a single antihypertensive agent can effectively reduce blood pressure in only a limited number of patients, while most require therapy with two or more agents to achieve target levels. As initial therapy, American and European guidelines suggest a combination of two antihypertensive drugs and the use of a third antihypertensive drug when hypertension is still uncontrolled. Initial combination therapy is recommended in high-risk patients for an immediate blood pressure response, improved tolerability and possibly increased patient adherence. In addition to the potential benefits of combining different drug classes with synergistic pharmacological and physiological actions, this approach is useful for increasing the patient compliance with treatment, in particular if provided at fixed doses in a single pill. The minimisation of side effects is critical for the long-term treatment of a largely asymptomatic condition such as systemic hypertension. Low-dose combinations of different drugs from classes with complementary actions may provide the best ratio of lower side effects and improved tolerability with a significant blood pressure reduction, particularly in high-risk patients. This approach could be aided by a multidisciplinary lifestyle intervention on risk factors.

Occurrence of atrial fibrillation in pacemaker patients and its association with sleep apnea and heart rate variability.

AIMS: Sleep apnea (SA) is a risk factor for atrial fibrillation (AF) occurrence. Sympathovagal imbalance is a mechanism that predisposes to the development of AF and that occurs in SA. Some pacemakers can detect SA events and continuously measure a time domain measure of heart rate variability (HRV), i.e. the standard deviation of 5-min median atrial-atrial sensed intervals (SDANN). We evaluated the association between the occurrence of AF and device-detected SA and SDANN in patients who received pacemakers. METHODS: We enrolled 150 consecutive patients undergoing implantation of a dual-chamber pacemaker, capable of SA and SDANN estimation. The SA was defined as severe if the Respiratory Disturbance Index was ≥30 episodes/h for at least one night during the first week after implantation. RESULTS: Sixteen patients in permanent AF were excluded from our analysis. During follow-up, AF (cumulative device-detected AF duration > 6 h/day) occurred in 24(18%) patients out of the remaining 134 patients. Severe SA was detected in 84 patients. SDANN values were available in 74 patients and the median value was 76 ms [25°-75°percentile:58-77]. The risk of AF was higher in patients with severe SA (log-rank test; p = .033). The presence of either or both conditions (severe SA and SDANN < 76 ms) was associated with shorter time to AF event (p = .042) and was an independent predictor of AF (hazard ratio: 2.37; 95%CI:1.08 to 5.21; p = .033). CONCLUSION: In pacemaker patients, device-diagnosed severe SA and reduced SDANN are associated with a higher risk of AF.

Exercise training in patients with pulmonary and systemic hypertension: A unique therapy for two different diseases.

Pulmonary hypertension is a potentially life-threatening condition. Given its evolving definition, the incidence and prevalence of the disease is difficult to define, but registries suggest an increased global awareness. The management of patients with pulmonary arterial hypertension is highly specialised and requires multi-disciplinary input from a range of healthcare professionals, including cardiologists, respiratory physicians, rheumatologists, rehabilitation physicians and cardio-pulmonary physiotherapists. Historically, exercise training in pulmonary hypertension has not been recommended because of safety concerns. However, an increasing number of studies have demonstrated the benefit of exercise training on exercise capacity, peak oxygen consumption and quality of life. Systemic hypertension is one of the most important risk factors for cardiovascular disease, and has been ranked as the leading cause for death and disability worldwide: therefore, adequate control of blood pressure is important for public health. Lowering of blood pressure and prevention of hypertension is in first instance preferable by lifestyle changes. These include weight loss, moderation of alcohol intake, a diet with increased fresh fruit and vegetables, reduced saturated fat, reduced salt intake, reduced stress, and, finally, increased physical activity. With regard to the latter, former guidelines predominantly recommended aerobic exercises such as walking, jogging, and cycling for lowering blood pressure. The main focus of this narrative overview paper is to briefly examine and summarize the benefit of exercise training in patients with pulmonary and systemic hypertension, suggest mechanisms by which exercise may improve symptoms and function and provide evidence-based recommendations regarding the frequency and intensity of exercise in these patients.

Pulmonary hypertension and exercise training: a synopsis on the more recent evidences.

The benefits of exercise training in virtually all humans, including those with a clinically stable chronic disease are numerous. The potential value lies in the fact that functional capacity is oftentimes significantly compromised. Exercise training not only play a role in reversing some of the pathophysiologic processes associated with chronic diseases but also improves clinical trajectory. Given the significant pathologic consequences associated with pulmonary hypertension and its implications for deteriorating right ventricular function as well as the perceived potential for a precipitous and possibly critical drop in cardiac output during periods of physical exertion, exercise training was historically not recommended for these patients. More recently, a promising body of literature demonstrating the safety and efficacy of exercise training (with benefit on exercise capacity, peak oxygen consumption and quality of life) in pulmonary hypertension patients has emerged, but the conclusion about the effects of exercise training were non-exhaustive and therefore there is still a lack of knowledge regarding exercise training for these patients. Thus, we aim to ascertain the current effectiveness of exercise rehabilitation for pulmonary hypertension by performing a brief overview on the latest currently available evidences in such an "at a glance" synopsis addressed to summarize/quantify the more recent existing body of literature. KEY MESSAGES Exercise training was historically not recommended in pulmonary hypertension. Recently, exercise training safety-efficacy in pulmonary hypertension has emerged. Exercise training should be recommended in addition to optimal medical therapy.

Antithrombotic Therapy After Percutaneous Coronary Intervention in Atrial Fibrillation: The Triple Trouble.

One of the most common conundrums in all cardiovascular medicine pertains to the care of patients with atrial fibrillation after percutaneous coronary intervention, because of both dual antiplatelet therapy and oral anticoagulant therapy would seem to be necessary to reduce risks of stent thrombosis and thromboembolism, respectively, but also with an inevitable trade-off of more bleeding. Patients who require triple therapy are at high risk of both ischaemia and bleeding; therefore, defining a personalised secondary prevention strategy aimed at achieving the best net clinical benefit is essential. The good news is that we have entered an era of increased perceived and tangible safety that applies to both non-vitamin K-antagonist oral anticoagulants and newer drug-eluting stents. Even if the consistency across the major trials and the significantly lower risk of bleeding with dual therapy make it hard to argue that triple therapy should be used routinely, the aggregate evidence suggests that the net clinical benefit of dual therapy should give cardiologists confidence to drop aspirin when they are using a contemporary percutaneous coronary intervention strategy with drug-eluting stents. Waiting for more randomised trials and meta-analyses, for the time being, in patients not in clinical trials, full-dose oral triple therapy with dual antiplatelet agents and full-dose anticoagulation should be avoided as a routine practice, and the choice of the proper, that is, safer, oral anticoagulant, namely a non-vitamin K-antagonist oral anticoagulant, may be regarded by now as an additional bleeding avoiding strategy in patients with atrial fibrillation undergoing percutaneous coronary intervention.

Prevalence and clinical significance of left bundle branch block according to classical or strict definition criteria in permanent pacemaker patients.

BACKGROUND: Previous studies have shown that the presence of left bundle branch block (LBBB) is associated with an increased risk of cardiac mortality and heart failure (HF). Recently, new criteria to define strict LBBB have been proposed: QRS duration ≥140 ms for men and ≥130 ms for women, along with mid-QRS notching or slurring in ≥2 contiguous leads. HYPOTHESIS: We assessed the prevalence and prognostic significance of LBBB according to classical (QRS duration ≥120ms) and strict criteria in permanent pacemaker patients. METHODS: We retrospectively enrolled 723 consecutive patients who had undergone single- or dual-chamber pacemaker implantation at the study center from July 2002 to December 2014. Patients with a left ventricular ejection fraction ≤35% or a prior diagnosis of HF were excluded. RESULTS: LBBB was reported in 54 (7%) patients, and strict-LBBB in 15 (2%) patients. During a median follow-up of 48 months (range, 18-92 months), 147 (20%) patients reached the combined endpoint of death or HF hospitalization. Patients with LBBB and those with strict-LBBB displayed significantly higher rates of death or HF hospitalization (log-rank test, all P < 0.0001). In particular, strict-LBBB was associated with the worst outcome. The presence of LBBB according to classical definition criteria (hazard ratio [HR] = 1.98, confidence interval [CI]: 1.23-3.19, P = 0.005) and to strict criteria (HR = 2.20; CI: 1.04-4.65; P = 0.039) were both confirmed as independent predictors of death or HF hospitalization after adjustment for relevant clinical covariates. CONCLUSIONS: Among patients who had undergone standard pacemaker implantation, the prevalence of LBBB was 7% according to classical definition criteria and 2% according to strict criteria. The presence of LBBB, and particularly of strict-LBBB, at the baseline predicted a poor outcome in terms of death or HF hospitalization.

Hypertensive response to exercise and exercise training in hypertension: odd couple no more.

The diagnostic and prognostic implication of exaggerated blood pressure response to exercise has been controversial, with opinions ranging from a benign process to a harbinger of potential cardiovascular morbidity. Nonetheless, lowering of blood pressure and prevention of hypertension is in first instance preferable by lifestyle changes, and many studies have shown the inverse association between physical activity level and the incidence of cardiovascular diseases suggesting low aerobic fitness as a strong predictor for future cardiovascular disease and all-cause mortality in both healthy and cardiovascular disease patients, including those with hypertension. Endothelial function, large artery stiffness and neurohormonal response are surely implicated both in the development of exaggerated blood pressure response to exercise and in the positive effect of physical exercise in the prevention and management of hypertension and cardiovascular disease in general. In their interesting and well documented review published in this issue Kim and Ha broadly described the possible pathophysiologic mechanisms of exaggerated blood pressure response to exercise and its clinical implications: in this regard, a very interesting issue could be represented by the role of exercise training. In fact, there is an the ample evidence in the literature that physical activity could positively affect endothelial function, arterial stiffness, neurohormonal response and finally blood pressure levels both in healthy men and in hypertensive patients and so should be considered a very important element in the prevention and management of cardiovascular disease.

The relationship between obesity and hypertension: an updated comprehensive overview on vicious twins.

Obesity is a growing global health concern, with a rapid increase being observed in morbid obesity. Obesity is associated with an increased cardiovascular risk and earlier onset of cardiovascular morbidity. The growing obesity epidemic is a major source of unsustainable health costs and morbidity and mortality because of hypertension, type 2 diabetes mellitus, dyslipidemia, certain cancers and major cardiovascular diseases. Similar to obesity, hypertension is a key unfavorable health metric that has disastrous health implications: currently, hypertension is the leading contributor to global disease burden, and the direct and indirect costs of treating hypertension are exponentially higher. Poor lifestyle characteristics and health metrics often cluster together to create complex and difficult-to-treat phenotypes: excess body mass is such an example, facilitating a cascade of pathophysiological sequelae that create such as a direct obesity-hypertension link, which consequently increases cardiovascular risk. Although some significant issues regarding assessment/management of obesity remain to be addressed and the underlying mechanisms governing these disparate effects of obesity on cardiovascular disease are complex and not completely understood, a variety of factors could have a critical role. Consequently, a comprehensive and exhaustive investigation of this relationship should analyze the pathogenetic factors and pathophysiological mechanisms linking obesity to hypertension as they provide the basis for a rational therapeutic strategy in the aim to fully describe and understand the obesity-hypertension link and discuss strategies to address the potential negative consequences from the perspective of both primordial prevention and treatment for those already impacted by this condition.