Clinical considerations and pathophysiological associations among obesity, weight loss, heart failure, and hypertension.

PURPOSE OF REVIEW: To describe the relationship between three pandemics: hypertension, obesity, and heart failure. From pathophysiology to treatment, understanding how these disease entities are linked can lead to breakthroughs in their prevention and treatment. The relevance of this review lies in its discussion of novel pharmacological and surgical treatment strategies for obesity and hypertension, and their role in the prevention and treatment of heart failure. RECENT FINDINGS: Novel medications such as GLP-1 agonists have demonstrated sustained weight loss in patients with obesity, and concurrent improvements in their cardiometabolic profile, and possibly also reductions in hypertension-related comorbidities including heart failure. Surgical therapies including laparoscopic bariatric surgery represent an important treatment strategy in obese patients, and recent studies describe their use even in patients with advanced heart failure, including those with ventricular assist devices. SUMMARY: These developments have deep implications on our efforts to understand, mitigate, and ultimately prevent the three pandemics, and offer promising improvements to quality of life, survival, and the cost burden of these diseases.

Bariatric Surgery in Patients with Obesity and Ventricular Assist Devices Considered for Heart Transplantation: Systematic Review and Individual Participant Data Meta-analysis.

BACKGROUND: Class II obesity (body mass index BMI ≥35 kg/m2) is a contraindication to heart transplantation (HT). Although few single-center studies (case reports/series and small cohorts) have reported promising outcomes of bariatric surgery (BS) in patients with obesity and ventricular assist devices, low sample sizes have made their analysis and interpretation challenging. METHODS AND RESULTS: We conducted a systematic search in ClinicalTrials.gov, Cochrane, Embase, PubMed, Google Scholar, and most relevant bariatric and heart failure journals. We extracted baseline and outcome individual participant data for every ventricular assist device patient undergoing BS with reported postoperative BMI and their respective timepoints when BMI data were measured. Fourteen references with 29 patients were included. The mean age was 41.9 ± 12.2 years, 82.8% underwent laparoscopic sleeve gastrectomy, and 39.3% had reported perioperative adverse events. The mean pre-BS BMI was 45.5 ± 6.6 kg/m2 and decreased significantly during follow-up (rho -0.671; P< .00001). Among 23 patients with documented listing status, 78.3% were listed for HT. Thirteen of 28 patients (46.4%) underwent HT at 14.4 ± 7.0 months. There were no reported deaths for the HT-free 1-year period. Median follow-up was 24 months (interquartile range, 12-30 months). Twenty-two of 28 patients (78.6%) achieved the composite outcome (BMI of<35 kg/m2/HT/listing for HT/myocardial recovery) at 11 months (interquartile range, 3-17 months). Patients with a BMI<45 kg/m2 had a higher chance of achieving the composite outcome (P< .003). CONCLUSIONS: BS may help patients with obesity and ventricular assist devices to lose a significant amount of weight and improve their candidacy for HT or even achieve myocardial recovery.

First in human: the effects of biventricular pacing on cardiac output in severe pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) carries high morbidity and mortality despite available treatment options. In severe PAH, right ventricular (RV) diastolic pressure overload leads to interventricular septal bowing, hindering of left ventricular diastolic filling and reduced cardiac output (CO). Some animal studies suggest that pacing may mitigate this effect. We hypothesized that eliminating late diastole via ventricular pacing could improve CO in human subjects with severe PAH. Using minimal to no sedation, we performed transvenous acute biventricular (BiV) pacing and right heart catheterization in six patients with symptomatic PAH. Hemodynamic measurements were taken at baseline and during BiV pacing at various 20-ms intervals of V-V timing. We compared baseline CO to (1) CO while pacing the RV first by 80 ms (mimicking RV-only pacing), and then to (2) CO during pacing at the V-V timing that resulted in the highest CO. All participants were female, PASP 74 ± 14 mmHg, QRS duration 104 ± 20 ms. Compared with baseline, the CO decreased when the RV was paced first by 80 ms (7.2 ± 1.0 vs. 6.2 ± 1.1 L/min, p = 0.028). Pacing with optimal V-V timing produced CO similar to baseline (7.2 ± 1.0 vs. 7.4 ± 1.4, p = 0.92). Two patients (33%) met the predefined endpoint of a 15% increase in CO during pacing at the optimal V-V timing. In symptomatic PAH, V-V optimized acute BiV pacing does not consistently improve CO. However, acute BiV pacing did improve CO in a subset of this cohort. Further research is needed to identify predictors of response to cardiac resynchronization therapy in this population.

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.

Sarcoidosis-Associated Pulmonary Hypertension: An Updated Review and Discussion of the Clinical Conundrum.

Pulmonary hypertension (PH) is a life-threatening disease with complex pathophysiology. The World Health Organization has classified PH in 5 groups according to etiology, the fifth of which corresponds to PH due to unknown or multiple mechanisms; including sarcoidosis-associated PH (SAPH). Although this system has been used to guide treatment recommendations according to each group, it does not provide much insight into the heterogeneous group 5. Furthermore, pulmonary vasodilators have been contraindicated for patients in this cluster which represents a challenge for the management of SAPH which can sometimes improve with these PH-directed drugs. In this review, we discuss the classification of SAPH; as well as the evidence behind the use of pulmonary vasodilator, invasive procedures, and lung transplantation for treating SAPH; and the little that is known about his disease in the setting of cardiac sarcoidosis.

Elusive Diagnosis of Eosinophilic Myocarditis: A Case Series.

We present 2 relevant cases of eosinophilic myocarditis (EM) in patients that presented with cardiogenic shock, one of whom received a durable ventricular assist device followed by heart transplantation, with the diagnosis of EM being made based on analysis of the excisional biopsy obtained during implantation of the ventricular assist device. The second patient was initially misdiagnosed with peripartum cardiomyopathy and underwent abortion, to later being diagnosed with EM through endomyocardial biopsy. These two cases highlight the importance of high clinical suspicion for EM based on eosinophilia, comorbidities, and presentation, as well as the value of early diagnosis and therapeutic interventions, including corticosteroids, and advanced heart failure therapies, such as mechanical circulatory support and heart transplantation.

Characteristics and Outcomes of Pulmonary Angioplasty With or Without Stenting for Sarcoidosis-Associated Pulmonary Hypertension: Systematic Review and Individual Participant Data Meta-Analysis.

BACKGROUND: Pulmonary angioplasty has been performed in patients with sarcoidosis-associated pulmonary hypertension (SAPH) but most evidence comes from case reports and small case series. Overall outcomes remain unclear. We conducted an individual participant data (IPD) meta-analysis of baseline, procedural, and outcome data of pulmonary angioplasty in patients with SAPH. METHODS: We performed searches and systematically reviewed references from PubMed, Embase, Cochrane, ClinicalTrials.gov, and grey literature. We included IPD of patients who underwent pulmonary angioplasty for SAPH. Those without definitive diagnosis of sarcoidosis or with other causes of pulmonary vascular stenosis or compression were excluded. RESULTS: Of 1293 screened references, 7 were included. IPD was obtained for 17 patients (mean age 58.6 (±9.1) years; 82.4% female); most of whom were Scadding stages III or IV and had NYHA FC III or IV. All patients with documented changes in 6-minute-walk distance (6MWD) had a significant improvement that ranged from 12.6 to 102.4% (P < 0.01). There were no deaths during a median follow-up of 6 (3-18) months. CONCLUSIONS: Pulmonary angioplasty with or without stenting of focal stenosis or compressions of pulmonary vessels may lead to significant improvement in 6MWD in patients with SAPH. However, this study had a small sample and some methodological limitations, such as analysis mostly of case reports and series. Randomized controlled clinical trials and/or large multicenter registry studies are needed to provide higher evidence in this topic.

Rabbit Antithymocyte Globulin Induction in Heart Transplant Recipients at High Risk for Rejection.

Background: Induction with lymphocyte-depleting antibodies may improve allograft outcomes in heart transplant recipients who are at high immunologic risk for rejection. Methods: We conducted a single-center retrospective cohort study that compared outcomes between adult patients receiving rabbit antithymocyte globulin (rATG) induction vs no induction from 2011 through 2017. Key exclusion criteria were patients who did not receive tacrolimus and mycophenolate and patients who did not meet high immunologic risk criteria. Results: A total of 50 patients were included in the analysis. At 1 year, the composite primary outcome of ≥2R rejection as defined by the International Society for Heart and Lung Transplantation, any treated rejection, development of cardiac allograft vasculopathy, or graft loss was not different between groups (P=0.474). Serious infections were also similar between groups (P=0.963). In accordance with institutional guidelines, prednisone exposure was decreased in the rATG induction group at 1 month (24.04 mg ± 13.74 vs 35.18 mg ± 16.95; P=0.014). Conclusion: These results suggest that while rATG induction does not improve heart allograft outcomes, it may enable reducing early corticosteroid exposure in patients at high immunologic risk.

Laparoscopic Sleeve Gastrectomy in Patients with Obesity and Ventricular Assist Devices: a Comprehensive Outcome Analysis.

We analyzed in detail the outcomes of eight patients with ventricular assist devices (VADs) and obesity who underwent laparoscopic sleeve gastrectomy (LSG) at a single heart transplant (HT) center. This comprehensive analysis included body mass index (BMI) trends from VAD implantation to the time of LSG; BMI and percentage of excess BMI lost during follow-up; adverse outcomes; and changes in echocardiographic parameters, fasting lipids, unplanned hospitalizations, and functional status. We also identified the patients who achieved the following outcomes: listing for HT, HT, 50% excess BMI loss, and BMI < 35 kg/m2. Laparoscopic sleeve gastrectomy seems to be a reasonable and effective intervention to help patients with VADs and obesity to decrease excess BMI and become candidates for HT.

Pulmonary Hypertension: A Brief Guide for Clinicians.

Pulmonary hypertension (PH) is classified into 5 clinical subgroups: pulmonary arterial hypertension (PAH), PH due to left-sided heart disease, PH due to chronic lung disease, chronic thromboembolic PH (CTEPH), and PH with an unclear and/or multifactorial mechanisms. A range of underlying conditions can lead to these disorders. Overall, PH affects approximately 1% of the global population, and over half of patients with heart failure may be affected. Cardiologists are therefore likely to encounter PH in their practice. Routine tests in patients with symptoms and physical findings suggestive of PH include electrocardiography, chest radiography, and pulmonary function tests. Transthoracic echocardiography is used to estimate the probability of PH. All patients with suspected or confirmed PH, without confirmed left-sided heart or lung diseases, should have a ventilation-perfusion scan to exclude CTEPH. Right-sided heart catheterization is essential for accurate diagnosis and classification. All patients with PAH or CTEPH must be referred to a specialist center. Surgical pulmonary endarterectomy is the treatment of choice for eligible patients with CTEPH. Targeted treatments (phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin analogues, and prostacyclin receptor agonists) are licensed for patients with PAH. The soluble guanylate cyclase stimulator riociguat is the only licensed targeted therapy for patients with inoperable or persistent/recurrent CTEPH. Management of PH resulting from left-sided heart disease primarily involves treatment of the underlying condition.

Laparoscopic sleeve gastrectomy in obese patients with ventricular assist devices: a data note.

OBJECTIVES: Patients with end-stage heart failure (ESHF) treated with ventricular assist devices (VADs) tend to gain weight after implantation, which is associated with higher complication rates and is a contraindication for heart transplantation (HT). The objective was to analyze the outcomes of obese patients with ESHF and VADs who underwent laparoscopic sleeve gastrectomy (LSG) at Ochsner Medical Center in New Orleans, which is the only program performing VADs and HT in the State of Louisiana, and also one of the largest VAD centers in the USA. DATA DESCRIPTION: This dataset contains detailed baseline, perioperative, and long-term data of patients with VADs undergoing LSG. These variables were collected retrospectively from electronic medical records. Patients who achieved ≥ 50% excess BMI loss, BMI ≤ 35 kg/m2, listing for HT, HT, or myocardial recovery were identified and the timing to each of these milestones was documented. These data can be used alone or in combination with other datasets to achieve a larger sample size with more power for further analysis of these variables, which include the most important, standard, and objective bariatric and ESHF outcomes of patients with VADs undergoing LSG. Elaboration of composite outcomes is feasible.

Bariatric surgery in obese patients with ventricular assist devices.

OBJECTIVES: Patients with end-stage heart failure (ESHF) treated with ventricular assist devices (VADs) tend to gain weight, which may prevent them from receiving heart transplantation (HT) if their body mass index (BMI) reaches ≥ 35 kg/m2. The objective was to synthesize all cases available in the literature and describe the most important outcomes of bariatric surgery (BS) in VAD patients, including BMI trends, reaching a BMI < 35 kg/m2, listing for HT, achieving HT, myocardial recovery, and mortality. These data were obtained for an individual participant data (IPD) meta-analysis and include available IPD for every case in the scientific literature describing VAD patients undergoing BS during VAD support with documented postoperative BMI (and time of measurement) during follow-up. DATA DESCRIPTION: These data include baseline, periprocedural, and long-term outcomes for the 29 patients meeting selection criteria. The composite outcome includes reaching a BMI < 35 kg/m2, listing for HT, receiving HT, and myocardial recovery, indicating significant BMI loss associated with major ESHF outcomes. As multiple centers are becoming more experienced in this field, the present data can be merged with their databases to form larger samples that will allow to perform further statistical analysis to identify outcome predictors and improve clinical protocols and outcomes.

Use of TandemHeart as Bridge to Recovery for Antibody-Mediated Rejection in a Heart Transplant Patient.

Antibody-mediated rejection is a major cause of graft failure, mortality, and morbidity among cardiac transplant recipients. We present the first reported case of TandemHeart (LivaNova, Pittsburgh, Pennsylvania) used in the management of antibody-mediated rejection associated with cardiogenic shock. (Level of Difficulty: Advanced.).

Sexual activity and chronic heart failure.

Little has been published about sexual function in chronic heart failure (CHF) and knowledge among clinicians in this regard is sparse. To review data regarding sexual function and dysfunction in patients with CHF, 2 of the authors (S.A.M. and P.A.U.) independently conducted a literature search using the MEDLINE database. English-language articles and cited bibliographies published between January 1996 and November 2006 were reviewed. Search terms included heart failure or CHF or ventricular dysfunction or heart disease in conjunction with sexual activity, erectile dysfunction, impotence, or sex. Articles were selected for inclusion if they had a primary focus on CHF and sexual function or dysfunction. Critical reviews of the literature, observational studies using self-reported patient surveys, and prospective, blinded, randomized, placebo-controlled trials were included. Articles were not excluded on the basis of patient sample size but were excluded if the article concerned a broad aspect of cardiovascular disease rather than CHF. When properly screened and treated, most patients with CHF can safely engage in sexual activity and be treated for erectile dysfunction with sildenafil, provided that they do not have active ischemia and do not require treatment with nitrates. Clinicians should know the physiological requirements of sexual activity and the impact CHF has on sexual performance. Fear of a cardiac event during intercourse can interfere with patients' ability to perform and enjoy sex, and so it is important that the physician be able to counsel patients with CHF about sexual activity.

Breaking Down the Barriers: Why the Delay in Referral for Pulmonary Arterial Hypertension?

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare and fatal disease. While many treatment options have been shown to improve quality of life, exercise tolerance, and hemodynamics in PAH, survival remains poor, in part due to the advanced stage at which patients present to PAH specialists. METHODS: This perspective paper explores challenges related to the timing of referral, diagnosis, and initiation of therapy. RESULTS: Multiple factors account for the delay in referral, including fallacies in physician education, commercial influence resulting in inappropriate prescribing practices, and barriers in access to care. CONCLUSION: Improving physician education, encouraging the prescription of PAH medications to be done predominantly by PAH specialists, overcoming barriers to care, and promoting screening for PAH will help ensure early referral, diagnosis, and treatment.

Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision.

BACKGROUND: Outcomes of traditional mechanical support paradigms (extracorporeal membrane oxygenation, intraaortic balloon pump [IABP], and permanent left ventricular assist device [LVAD]) in acute decompensated heart failure have generally been suboptimal. Novel approaches, such as minimally invasive LVAD therapy (Impella 5.0 device), promise less invasive but equivalent hemodynamic support. However, it is yet unknown whether the outcomes with such devices support widespread acceptance of this new technology. We recently started utilizing the right subclavian artery (RSA) for Impella 5.0 implantation and report our early experience and outcomes with this novel approach. METHODS: A single-center retrospective review was performed of 24 patients with acute on chronic decompensated heart failure who received the Impella 5.0 via the RSA from June 2011 to May 2014. The device was implanted via a cutdown through an 8-mm vascular graft sewn to the RSA. The device was positioned with fluoroscopy and transesophageal echocardiography. RESULTS: The mean age of the patients was 51.29 years, and 75% were male. At implantation, all patients were mechanically ventilated on at least 2 inotropes with persistent cardiogenic shock, and 17 (70.8%) were on IABP support. Postimplantation, 21 (87.5%) tolerated extubation, and all 17 of the patients with IABPs tolerated discontinuation of IABP support. The reduction in the Model for End-Stage Liver Disease score preimplantation vs postimplantation was statistically significant (21.17 vs 14.88, P=0.0014), suggesting improvement in end organ function. A significant decrease was also seen in creatinine levels before and after implantation (2.17 mg/dL vs 1.50 mg/dL, P=0.0043). The endpoint of support included recovery in 6 patients (25.0%), permanent LVAD in 9 (37.5%), and heart transplantation in 2 (8.3%). Death occurred in 7 patients (29.2%) as a result of multisystem organ failure, infection, or patient withdrawal of care. CONCLUSION: Minimally invasive LVAD therapy using the Impella 5.0 via the RSA cutdown is an attractive option in acute on chronic decompensated heart failure. Improvement in end organ function allows for transition to recovery or to advanced surgical therapies such as permanent LVAD and heart transplantation. Significant advantages to this approach include improved left ventricular unloading, lower anticoagulation need, and the potential for ambulation and physical therapy.

Pulmonary arterial hypertension: progress and challenges in the modern treatment era.

Pulmonary arterial hypertension (PAH) is a chronic, progressive disease with an estimated incidence of 2 cases per million individuals per year and a prevalence of approximately 10 to 15 cases per million individuals. PAH is more common in certain groups of patients, such as those with connective tissue disease and congenital heart disease, and is often overlooked in patients with these comorbidities. Treatment options in the United States have expanded to include 12 PAH-specific therapies, 3 of which were approved in 2013. As a result of treatment advancements, PAH patients are living longer. However, many challenges remain. Resource utilization in PAH, a primary driver of which is hospitalization, imposes a major economic burden on patients, payers, and society. Because change in 6-minute walk distance and other historical measures do not correlate well with the risk of hospitalization, guidelines favor more rigorous composite assessments of efficacy that take into account clinical worsening, including mortality and hospitalization. Stakeholders, including providers and payers, are tasked with selecting treatments with the best evidence of clinical benefit. Managing adherence to those therapies remains an important priority in improving clinical outcomes and reducing the overall clinical and economic burden of PAH. Future research that includes patient-reported outcomes, particularly those that reflect health-related quality of life, may be of particular relevance in this complex disease.