Resetting the neurohormonal balance in heart failure (HF). the relevance of the natriuretic peptide (NP) system to the clinical management of patients with HF

The natriuretic peptide (NP) system, which includes atrial natriuretic peptide, B-type natriuretic peptide, and C-type natriuretic peptide, has an important role in cardiovascular homeostasis, promoting a number of physiological effects including diuresis, vasodilation, and inhibition of the renin-angiotensin-aldosterone system. Heart failure (HF) is associated with defects in NP processing and synthesis, and there is a strong relationship between NP levels and disease state. NPs are useful biomarkers in HF, and their use in diagnosis and evaluation of prognosis is well established, particularly in patients with HF with reduced ejection fraction (HFrEF). There has also been interest in their use to guide disease management and therapeutic decision making. An understanding of NPs in HF has also resulted in interest in synthetic NPs for the treatment of HF and in treatments that target neprilysin, a protease that degrades NPs. A novel drug, the angiotensin receptor neprilysin inhibitor sacubitril/valsartan (LCZ696), which simultaneously inhibits neprilysin and blocks the angiotensin II type I receptor, was shown to have a favorable efficacy and safety profile in patients with HFrEF and has been approved for use in such patients in Europe and the USA. In light of the development of treatments that target neprilysin and of recent data in relation to synthetic NPs, it is timely to review the current understanding of the role of NPs in HF and their use in diagnosis, evaluating prognosis and guiding treatment, as well as their place in HF therapy

The marfan syndrome: Abnormal aortic elastic properties

Aortic distensibility and aortic stiffness index were measured at the ascending aorta (3 cm above the aortic valve) and the mid-portion of the abdominal aorta from the changes in echocardiographic diameters and pulse pressure in 14 patients with the Marfan syndrome and 15 age- and gender-matched normal control subjects. The following formulas were used: 1) Aortic distensibility = 2(Changes in aortic diameter)/(Diastolic aortic diameter) (Pulse pressure); and 2) Aortic stiffness index = ln(Systolic blood pressure)/(Diastolic blood pressure)(Changes in aortic diameter)/Diastolic aortic diameter. Pulse wave velocity was also measured.Compared with normal subjects, patients with the Marfan syndrome had decreased aortic distensibility in the ascending and the abdominal aorta (2.9 ± 1.3 vs. 5.6 ± 1.4 cm2 dynes-1, p < 0.001 and 4.5 ± 2.1, vs. 7.7 ± 2.5, cm2 dynes-1, p < 0.001, respectively) and had an increased aortic stiffness index in the ascending and the abdominal aorta (10.9 ± 5.6 vs. 5.9 ± 2.2, p < 0.005 and 7.1 ± 3.1 vs. 3.9 ± 1.2, p < 0.005, respectively). Aortic diameters in the ascending aorta were larger in these patients than in normal subjects, but those in the abdominal aorta were similar in the two groups. Linear correlations for both aortic distensibility and stiffness index were found between the ascending and the abdominal aorta (r = 0.85 and 0.71, respectively). Pulse wave velocity was more rapid in the patients than in the normal subjects (11.6 ± 2.5 vs. 9.5 ± 1.4 m/s, respectively, p < 0.01).Thus, aortic elastic properties are abnormal in patients with the Marfan syndrome irrespective of the aortic diameter, which suggests an intrinsic abnormality of the aortic arterial wall

The Sympathetic Nervous System in Heart Failure Physiology, Pathophysiology, and Clinical Implications

Heart failure is a syndrome characterized initially by left ventricular dysfunction that triggers countermeasures aimed to restore cardiac output. These responses are compensatory at first but eventually become part of the disease process itself leading to further worsening cardiac function. Among these responses is the activation of the sympathetic nervous system (SNS) that provides inotropic support to the failing heart increasing stroke volume, and peripheral vasoconstriction to maintain mean arterial perfusion pressure, but eventually accelerates disease progression affecting survival. Activation of SNS has been attributed to withdrawal of normal restraining influences and enhancement of excitatory inputs including changes in: 1) peripheral baroreceptor and chemoreceptor reflexes; 2) chemical mediators that control sympathetic outflow; and 3) central integratory sites. The interface between the sympathetic fibers and the cardiovascular system is formed by the adrenergic receptors (ARs). Dysregulation of cardiac beta1-AR signaling and transduction are key features of heart failure progression. In contrast, cardiac beta2-ARs and alpha1-ARs may function in a compensatory fashion to maintain cardiac inotropy. Adrenergic receptor polymorphisms may have an impact on the adaptive mechanisms, susceptibilities, and pharmacological responses of SNS. The beta-AR blockers and the inhibitors of the renin-angiotensin-aldosterone axis form the mainstay of current medical management of chronic heart failure. Conversely, central sympatholytics have proved harmful, whereas sympathomimetic inotropes are still used in selected patients with hemodynamic instability. This review summarizes the changes in SNS in heart failure and examines how modulation of SNS activity may affect morbidity and mortality from this syndrome

Cognitive Impairment in Heart Failure

Cognitive impairment (CI) is increasingly recognized as a common adverse consequence of heart failure (HF). Although the exact mechanisms remain unclear, microembolism, chronic or intermittent cerebral hypoperfusion, and/or impaired cerebral vessel reactivity that lead to cerebral hypoxia and ischemic brain damage seem to underlie the development of CI in HF. Cognitive decline in HF is characterized by deficits in one or more cognition domains, including attention, memory, executive function, and psychomotor speed. These deficits may affect patients' decision-making capacity and interfere with their ability to comply with treatment requirements, recognize and self-manage disease worsening symptoms. CI may have fluctuations in severity over time, improve with effective HF treatment or progress to dementia. CI is independently associated with disability, mortality, and decreased quality of life of HF patients. It is essential therefore for health professionals in their routine evaluations of HF patients to become familiar with assessment of cognitive performance using standardized screening instruments. Future studies should focus on elucidating the mechanisms that underlie CI in HF and establishing preventive strategies and treatment approaches

Totally Occlusive Diffuse In-stent Restenosis in Saphenous Vein Graft to Right Coronary Artery and Acute Coronary Syndrome

A 78-year-old gentleman presented with Canadian Cardiological Society (CCS) class III angina and had been getting excruciating substernal pain while walking 50 to 100 m on the flat over the last 15 days despite optimal medical therapy. From his past medical history the patient underwent CABG in 1997 (LIMA to LAD and SVG to dominant RCA); in 2006 he had an angioplasty done in his SVG and stents were implanted (no medical data regarding the angioplasty were found). Cardiac enzymes and troponin were negative; a mild increase of creatinine was noted on admission. The echocardiogram revealed severe basal inferior wall hypokinesia with overall reasonably preserved left ventricular and right ventricular systolic function... (excerpt

Left atrial size and function in a South Asian population and their potential influence on the risk of atrial fibrillation

Background: South Asians have a low prevalence of atrial fibrillation (AF) compared with Caucasians despite having a higher prevalence of conventional risk factors for the arrhythmia. The reason for this disparity is uncertain but may be due to ethnic differences in atrial morphology. This study examines the association between ethnicity and left atrial (LA) size and function in South Asian and Caucasian subjects using the reference technique of cardiovascular magnetic resonance imaging (MRI). Hypothesis: South Asians have smaller LA size and therefore increased LA function. Methods: Retrospective case‐control study of 60 South Asian and 60 Caucasian patients who had undergone a clinically indicated MRI between April 2010 and October 2017 and had been found to have a structurally normal heart. LA and left ventricular (LV) volume and function were assessed and compared between the ethnicities. Results: In comparison with Caucasians, South Asians had significantly lower minimum (27.7 ± 11.1 mL vs 34.9 ± 12.3 mL, P = 0.002) and maximum LA volumes (64.7 ± 21.1 mL vs 80.9 ± 22.5 mL, P < 0.001), lower LV end‐diastolic volume (P < 0.001), lower LV stroke volume (P < 0.001), and lower LV mass (P = 0.022) and these values remained significant after correcting for body surface area. Further analysis revealed that LA volume was independently associated with South Asian ethnicity. There was no difference in LA function between the ethnic groups. Conclusions: South Asians have reduced LA volumes and a proportionally smaller heart size in comparison to Caucasians. Smaller LA size may protect against the development of AF by reducing the risk of reentrant circuit formation and atrial fibrosis development

Assessment of Myocardial Viability in Ischemic Cardiomyopathy With Reduced Left Ventricular Function Undergoing Coronary Artery Bypass Grafting

Background: We aim to provide a comprehensive review of the current state of knowledge of myocardial viability assessment in patients undergoing coronary artery bypass grafting (CABG), with a focus on the clinical markers of viability for each imaging modality. We also compare mortality between patients with viable myocardium and those without viability who undergo CABG. Methods: A systematic database search with meta‐analysis was conducted of comparative original articles (both observations and randomized controlled studies) of patients undergoing CABG with either viable or nonviable myocardium, in EMBASE, MEDLINE, Cochrane database, and Google Scholar, from inception to 2022. Imaging modalities included were dobutamine stress echocardiography (DSE), cardiac magnetic resonance (CMR), single‐photon emission computed tomography (SPECT), and positron emission tomography (PET). Results: A total of 17 studies incorporating a total of 2317 patients were included. Across all imaging modalities, the relative risk of death post‐CABG was reduced in patients with versus without viability (random‐effects model: odds ratio: 0.42; 95% confidence interval: 0.29–0.61; p < 0.001). Imaging for myocardial viability has significant clinical implications as it can affect the accuracy of the diagnosis, guide treatment decisions, and predict patient outcomes. Generally, based on local availability and expertise, either SPECT or DSE should be considered as the first step in evaluating viability, while PET or CMR would provide further evaluation of transmurality, perfusion metabolism, and extent of scar tissue. Conclusion: The assessment of myocardial viability is an essential component of preoperative evaluation in patients with ischemic heart disease undergoing surgical revascularization. Careful patient selection and individualized assessment of viability remain paramount

Left atrial function in heart failure with preserved ejection fraction:a systematic review and meta-analysis

Aims Left atrial (LA) mechanical function may play a significant role in the development and progression of heart failure with preserved ejection fraction (HFpEF). We performed a systematic review and meta-analysis to evaluate association of impaired LA function with outcomes in HFpEF. Methods and results Multiple databases were searched for original studies measuring different phases of LA function in HFpEF patients. Comparative LA function between HFpEF patients and healthy controls was assessed by pooling weighted mean differences (WMD). Adjusted hazard ratios (HRs) with 95% confidence intervals were pooled to evaluate the prognostic utility of LA function. Twenty-two studies (2 trials, 20 observational) comprising 1974 HFpEF patients and 751 healthy controls were included. HFpEF patients had decreased LA reservoir [WMD = -12.21% (-15.47, -8.95); P <0.001], LA conduit [WMD = -5.68% (-8.56, -2.79); P <0.001], and pump [WMD = -11.07% (-14.81, -7.34); P <0.001] emptying fractions compared with controls. LA reservoir [WMD = -13.38% (-16.07, -10.68); P <0.001], conduit [WMD = -4.09% (-6.77, -1.42); P = 0.003], and pump [WMD = -3.53% (-4.47, -2.59); P <0.001] strains were also significantly lower in HFpEF patients. Decreased LA reservoir strain [HR 1.24 (1.02, 1.50); P = 0.03] was significantly associated with risk of composite all-cause mortality or heart failure hospitalization. Conclusions Impaired LA function appears to have diagnostic and prognostic value in HFpEF, but whether indices of LA function truly refine discrimination for diagnosis or prognosis remains to be fully determined. Larger studies are needed to better evaluate associations between LA function and clinical outcomes and the role of LA function as a target for novel HFpEF therapies