Obesity, Challenges, and Weight-Loss Strategies for Patients With Ventricular Assist Devices.

For adults with advanced heart failure, class II/III obesity (body mass index ≥35 kg/m2) represents major challenges, and it is even considered a contraindication for heart transplantation (HT) at many centers. This has led to growing interest in preventing and treating obesity to help patients with advanced heart failure become HT candidates. Among all weight-loss strategies, bariatric surgery (BSx) has the greatest weight loss efficacy and has shown value in enabling select patients with left ventricular assist devices (LVADs) and obesity to lose sufficient weight to access HT. Nevertheless, both BSx and antiobesity medications warrant caution in the LVAD population. In this review, the authors describe and interpret the available published reports on the impact of obesity and weight-loss strategies for patients with LVADs from general and HT candidacy standpoints. The authors also provide an overview of the journey of LVAD recipients who undergo BSx and review major aspects of perioperative protocols.

State of the art on angiotensin-neprilysin inhibitors.

Angiotensin receptor neprilysin inhibitor (ARNI) decreases renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous systems (SNS) activity promoting vasodilation, decreasing myocardial hypertrophy and fibrosis. Beyond the SNS, RAAS and natriuretic peptide systems, ARNI results in increased circulatory and myocardial nitric oxide levels activating cGMP and protein kinase G, which reduces oxidative stress, myocyte hypertrophy, cell death and has anti-thrombotic effects. ARNIs have a class I indication by heart failure (HF) guidelines in HFrEF patients with NYHA class II to III symptoms. Beyond HFrEF, the use of ARNIs has also been expanded to other clinical settings including HF with preserved ejection fraction (EF, HFpEF), acute HF, advanced HF, hypertension, arrhythmias and chronic kidney disease. This paper reviews the clinical benefits of ARNIs in both HF and the aforementioned cardiovascular conditions. We also discuss the combined use of ARNI with SGLT2i and their potential synergistic benefits on cardiovascular outcomes.

Utilization of coronary computed tomography angiography and computed tomography-derived fractional flow reserve in a critical limb-threatening ischemia cohort.

Objective: Patients with peripheral arterial disease (PAD) have a significant risk of myocardial infarction and death secondary to concomitant coronary artery disease (CAD). This is particularly true in patients with critical limb-threatening ischemia (CLTI) who exceed a 20% mortality rate at 6 months despite standard treatment with risk factor modification. Although systematic preoperative coronary testing is not recommended for patients with PAD without cardiac symptoms, the clinical manifestations of CAD are often muted in patients with CLTI due to poor mobility and activity intolerance. Thus, the true incidence and impact of "silent" CAD in a CLTI cohort is unknown. This study aims to determine the prevalence of ischemia-producing coronary artery stenosis in a CLTI cohort using coronary computed tomography angiography (cCTA) and computed tomography (CT)-derived fractional flow reserve (FFRCT), a noninvasive imaging modality that has shown significant correlation to cardiac catheterization in the detection of clinically relevant coronary ischemia. Methods: Patients presenting with newly diagnosed CLTI at our institution from May 2020 to April 2021 were screened for underlying CAD. Included subjects had no known history of CAD, no cardiac symptoms, and no anginal equivalent complaints at presentation. Patients underwent cCTA and FFRCT evaluation and were classified by the anatomic location and severity of CAD. Significant coronary ischemia was defined as FFRCT ≤0.80 distal to a >30% coronary stenosis, and severe coronary ischemia was documented at FFRCT ≤0.75, consistent with established guidelines. Results: A total of 170 patients with CLTI were screened; 65 patients (38.2%) had no coronary symptoms and met all inclusion/exclusion criteria. Twenty-four patients (31.2%) completed cCTA and FFRCT evaluation. Forty-one patients have yet to complete testing secondary to socioeconomic factors (insurance denial, transportation inaccessibility, testing availability, etc). The mean age of included subjects was 65.4 ± 7.0 years, and 15 (62.5%) were male. Patients presented with ischemic rest pain (n = 7; 29.1%), minor tissue loss (n = 14; 58.3%) or major tissue loss (n = 3; 12.5%). Significant (≥50%) coronary artery stenosis was noted on cCTA in 19 of 24 patients (79%). Significant left main coronary artery stenosis was identified in two patients (10%). When analyzed with FFRCT, 17 patients (71%) had hemodynamically significant coronary ischemia (FFRCT ≤0.8), and 54% (n = 13) had lesion-specific severe coronary ischemia (FFRCT ≤0.75). The mean FFRCT in patients with coronary ischemia was 0.70 ± 0.07. Multi-vessel disease pattern was present in 53% (n = 9) of patients with significant coronary stenosis. Conclusions: The use of cCTA-derived fractional flow reserve demonstrates a significant percentage of patients with CLTI have silent (asymptomatic) coronary ischemia. More than one-half of these patients have lesion-specific severe ischemia, which may be associated with increased mortality when treated solely with risk factor modification. cCTA and FFRCT diagnosis of significant coronary ischemia has the potential to improve cardiac care, perioperative morbidity, and long-term survival curves of patients with CLTI. Systemic improvements in access to care will be needed to allow for broad application of these imaging assessments should they prove universally valuable. Additional study is required to determine the benefit of selective coronary revascularization in patients with CLTI.

Animal models of postpartum hemorrhage.

Postpartum hemorrhage (PPH)-heavy bleeding following childbirth-is a leading cause of morbidity and mortality worldwide. PPH can affect individuals regardless of risks factors and its incidence has been increasing in high-income countries including the United States. The high incidence and severity of this childbirth complication has propelled research into advanced treatments and alternative solutions for patients facing PPH; however, the development of novel treatments is limited by the absence of a common, well-established and well-validated animal model of PPH. A variety of animals have been used for in vivo studies of novel therapeutic materials; however, each of these animals differs considerably from the anatomy and physiology of a postpartum woman, and the methods used for achieving a postpartum hemorrhagic condition vary widely. Here we critically evaluate the various animal models of PPH presented in the literature and propose additional and alternative methods for modeling PPH in in vivo studies. We highlight how current animal models successfully or unsuccessfully mimic the anatomy and physiology of a postpartum woman and how this may impact treatment development. We aim to equip researchers with the necessary background information to select appropriate animal models for their research related to PPH solutions, while supporting the goals of refinement, reduction and replacement (3Rs) in preclinical animal studies.

Discovery of circulating miRNAs as biomarkers of chronic Chagas heart disease via a small RNA-Seq approach.

Chagas disease affects approximately 7 million people worldwide in Latin America and is a neglected tropical disease. Twenty to thirty percent of chronically infected patients develop chronic Chagas cardiomyopathy decades after acute infection. Identifying biomarkers of Chagas disease progression is necessary to develop better therapeutic and preventive strategies. Circulating microRNAs are increasingly reliable biomarkers of disease and therapeutic targets. To identify new circulating microRNAs for Chagas disease, we performed exploratory small RNA sequencing from the plasma of patients and performed de novo miRNA prediction, identifying potential new microRNAs. The levels of the new microRNAs temporarily named miR-Contig-1519 and miR-Contig-3244 and microRNAs that are biomarkers for nonchagasic cardiomyopathies, such as miR-148a-3p and miR-224-5p, were validated by quantitative reverse transcription. We found a specific circulating microRNA signature defined by low miR-Contig-3244, miR-Contig-1519, and miR-148a-3 levels but high miR-224-5p levels for patients with chronic Chagas disease. Finally, we predicted in silico that these altered circulating microRNAs could affect the expression of target genes involved in different cellular pathways and biological processes, which we will explore in the future.

Outcomes of Patients With Left Ventricular Assist Devices Requiring Intermittent Hemodialysis: Single-Center Cohort, Systematic Review, and Individual-Participant Data Meta-Analysis.

Patients with left ventricular assist devices (LVADs) who require intermittent hemodialysis (iHD) are considered to have a poor prognosis despite a paucity of supportive evidence, mostly from small single-center cohorts and extrapolations from studies of patients who received continuous renal replacement therapy but no iHD. We conducted a systematic review and individual-participant-data meta-analysis of the literature including our single-center cohort to examine the outcomes of patients initiated on iHD following LVAD implantation. Sixty-four patients from 5 cohorts met selection criteria (age 57.5 [46-64.5] years, 87% HeartMate II, mostly bridge to transplantation). Follow-up after iHD initiation was 87.5 (38.5-269.5) days, although it was considerably longer in our center than in other cohorts (601.5 [93-1559] days vs 65 [26-180] days, P = 0.0007). The estimated median survival was 308 (76-912.5) days and varied significantly among cohorts, ranging from 60 (57-65) to 838 (103-1872) days (P = 0.0096). Twelve (18.8%) patients achieved either heart transplantation (HT) or remission during follow-up. Patients who received HT had an 8-fold longer estimated median survival (1972 [799-1972] days vs 244 [64-838] days, P = 0.0112). Being from a more recent cohort was associated with better 1-year survival. Renal recovery occurred in eight patients (13.1%) at 30 days and its cumulative incidence increased to 73% (27/37 patients with available data) at 1 year. Most patients initiated on iHD after LVAD experienced renal recovery within the first year after implantation. Improved survival was observed for patients who received HT and in those from more recent cohorts. Some patients were able to survive on LVAD and iHD support for several years.

Probabilistic reinforcement precludes transitive inference: A preliminary study.

In the basic verbal task from Piaget, when a relation of the form if A > B and B > C is given, a logical inference A > C is expected. This process is called transitive inference (TI). The adapted version for animals involves the presentation of a simultaneous discrimination between stimuli pairs. In this way, when A+B-, B+C-, C+D-, D+E- is trained, a B>D preference is expected, assuming that if A>B>C>D>E, then B>D. This effect has been widely reported using several procedures and different species. In the current experiment TI was evaluated employing probabilistic reinforcement. Thus, for the positive stimuli a .7 probability was administered and for the negative stimuli a .3 probability was administered. Under this arrangement the relation A>B>C>D>E is still allowed, but TI becomes more difficult. Five pigeons (Columba Livia) were exposed to the mentioned arrangement. Only one pigeon reached the criterion in C+D- discrimination, whereas the remaining did not. Only the one who successfully solved C+D- was capable of learning TI, whereas the others were not. Additionally, it was found that correct response ratios did not predict BD performance. Consequently, probabilistic reinforcement disrupted TI, but some positional ordering was retained in the test. The results suggest that TI might be affected by associative strength but also by the positional ordering of the stimuli. The discussion addresses the two main accounts of TI: the associative account and the ordinal representation account.

Secondary hypertension: evaluation and management.

PURPOSE OF REVIEW: Hypertension (HTN) that can be attributed to a particular source is known as secondary HTN (SH). Often, SH is difficult to control and thus referred to as resistant HTN, although the two terms are not mutually exclusive. RECENT FINDINGS: A common theme across several contributors to SH are coactivation of the sympathetic drive and hormonal changes, independent of hormonal axis activation. The key to effective management of SH is early recognition and treatment to avoid catastrophic cardiovascular disease effects and mortality. SUMMARY: This review article provides a contemporary summary of the conditions associated with SH and briefly reviews diagnostics and management.

Preimplant Hyponatremia Does Not Predict Adverse Outcomes in Patients With Left Ventricular Assist Devices.

Hyponatremia is a well-established marker of adverse outcomes in chronic heart failure (HF) but not well studied in patients with left ventricular assist device (LVAD). This is a retrospective study, single center study of HM3 [Abbott, USA] LVAD implants. We divided our population based on their sodium prior to LVAD implantation - hyponatremia if <135 mEq/L and normal sodium if 135-145 mEq/L. We compared postoperative and long-term outcomes. A total of 195 patients were included, preimplant hyponatremia was present in 40% with a sodium of 132.1 ± 2.1 vs 137.8 ± 1.9 mEq/L in the normal sodium group. No differences were observed in the postoperative or long-term outcomes. Preimplant hyponatremia was not associated with mortality or HF admissions, likely due to adequate left ventricular unloading and resolution of the mechanisms that lead to hyponatremia. These results suggest that optimization of mild hyponatremia may not be critical and should not delay LVAD placement.

Updates on obesity and the obesity paradox in cardiovascular diseases.

The prevalence of obesity has reached pandemic proportions worldwide and certainly in the United States. Obesity is a well-established independent risk factor for development of many cardiovascular diseases (CVD), including heart failure, coronary heart disease, atrial fibrillation, and hypertension. Therefore, it is logical to expect obesity would have a strong correlation with CVD mortality. However, a substantial body of literature demonstrates a paradox with improved prognosis of overweight and obese patients with established CVD compared to lean patients with the identical CVD. Surprisingly, similar data has also shown that cardiovascular fitness, rather than weight loss alone, influences the relationship between obesity and mortality in those with established CVD. The impact of fitness, exercise, physical activity (PA), and weight loss and their relationship to the obesity paradox are all reviewed here.

Diagnosis of tuberous sclerosis complex in adulthood: A case report.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder. TSC consists of a wide variety of clinical manifestations, with neurological and dermatological symptoms being the most frequent. This study aims to describe the clinical characteristics and management of a pregnant patient incidentally diagnosed with TSC.

The Impact of Obesity in Heart Failure.

Overweight and obesity adversely impact cardiac structure and function, affecting systolic and diastolic ventricular function. Epidemiologic studies have documented an obesity paradox in large heart failure cohorts, where overweight and obese individuals with established heart failure have a better short- and medium-term prognosis compared with leaner patients; this relationship is strongly impacted by level of cardiorespiratory fitness. There are implications for therapies aimed at increasing lean mass as well as weight loss and improvements in quality of diet for the prevention and treatment of heart failure and concomitant obesity to improve cardiorespiratory fitness.