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.

The use of diflunisal for transthyretin cardiac amyloidosis: a review.

Transthyretin cardiac amyloidosis (ATTR-CM) is caused by the accumulation of misfolded transthyretin (TTR) protein in the myocardium. Diflunisal, an agent that stabilizes TTR, has been used as an off-label therapeutic for ATTR-CM. Given limited data surrounding the use of diflunisal, a systematic review of the literature is warranted. We searched the PubMed, MEDLINE, and Embase databases for studies that reported on the use of diflunisal therapy for patients with ATTR-CM. We included English language studies which assessed the effect of diflunisal in adult patients with ATTR-CM who received diflunisal as primary treatment and reported clinical outcomes with emphasis on studies that noted the safety and efficacy of diflunisal in cardiac manifestations of ATTR amyloidosis. We excluded studies which did not use diflunisal therapy or used diflunisal therapy for non-cardiac manifestations of TTR amyloidosis. We also excluded case reports, abstracts, oral presentations, and studies with fewer than 10 subjects. Our search yielded 316 records, and we included 6 studies reporting on 400 patients. Non-comparative single-arm small non-randomized trials for diflunisal comprised 4 of the included studies. The 2 studies that compared diflunisal versus no treatment found improvements in TTR concentration, left atrial volume index, cardiac troponin I, and global longitudinal strain. Overall, diflunisal use was associated with decreased mortality and number of orthotopic heart transplant in ATTR-CM patients. Although a smaller number of patients had to stop treatment due to gastrointestinal side effects and transient renal dysfunction, there were no severe reactions reported in the studies included in our review. This systematic review supports the use of diflunisal for ATTR-CM. Additional long-term analyses and randomized clinical trials are needed to confirm these results.

Sex-Specific Prevalence, Incidence, and Mortality Associated With Atrial Fibrillation in Heart Failure.

OBJECTIVES: This study sought to investigate the mortality associated with atrial fibrillation (AF) in men and women with heart failure (HF) according to the sequence of presentation and rhythm versus rate control. BACKGROUND: The sex-specific epidemiology of AF in HF is sparse. METHODS: Using the Danish nationwide registries, all first-time cases of HF were identified and followed for all-cause mortality from 1998 to 2018. RESULTS: Among 252,988 patients with HF (mean age: 74 ± 13 years, 45% women), AF presented before HF in 54,064 (21%) and on the same day in 27,651 (11%) individuals, similar in women and men. Among patients without AF, the cumulative 10-year incidence of AF was 18.7% (95% confidence interval [CI]: 18.2% to 19.1%) in women and 21.3% (95% CI: 21.0% to 21.6%) in men. On follow-up (mean: 6.2 ± 5.8 years), adjusted mortality rate ratios were 3.33 (95% CI: 3.25 to 3.41) in women and 2.84 (95% CI: 2.78 to 2.90) in men if AF antedated HF, 3.45 (95% CI: 3.37 to 3.56) in women versus 2.76 (95% CI: 2.69 to 2.83) in men when AF and HF were diagnosed concomitantly, and 4.85 (95% CI: 4.73 to 4.97) in women versus 3.89 (95% CI: 3.80 to 3.98) in men when AF developed after HF. Compared with rate control for AF, a rhythm-controlling strategy was associated with lowered mortality in inverse probability-weighted models across all strata and in both sexes (hazard ratio: 0.75 to 0.83), except for women who developed AF after HF onset (hazard ratio: 1.03). CONCLUSIONS: More than half of all men and women with HF will develop AF during their clinical course, with prognosis associated with AF being worse in women than men. Further studies are needed to understand the underlying mechanisms.

Peak Systolic Blood Pressure During the Exercise Test: Reference Values by Sex and Age and Association With Mortality.

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The Association of Sleep Apnea and Cardiorespiratory Fitness With Long-Term Major Cardiovascular Events.

OBJECTIVE: To determine the risk of long-term major adverse cardiovascular events (MACE) when sleep-disordered breathing (SDB) and decreased cardiorespiratory fitness (CRF) co-occur. METHODS: We included consecutive patients who underwent symptom-limited cardiopulmonary exercise tests between January 1, 2005, and January 1, 2010, followed by first-time diagnostic polysomnography within 6 months. Patients were stratified based on the presence of moderate-to-severe SDB (apnea/hypopnea index ≥15 per hour) and decreased CRF defined as <70% predicted peak oxygen consumption (VO2). Long-term MACE was a composite outcome of myocardial infarction (MI), coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), stroke or transient ischemic attack (TIA), and death, assessed until May 21, 2018. Cox-proportional hazard models were adjusted for factors known to influence CRF and MACE. RESULTS: Of 498 included patients (60±13 years, 28.1% female), 175 (35%) had MACE (MI=17, PCI=14, CABG=13, stroke=20, TIA=12, deaths=99) at a median follow-up of 8.7 years (interquartile range=6.5 to 10.3 years). After adjusting for age, sex, beta blockers, systemic hypertension, diabetes mellitus, coronary artery disease, cardiac arrhythmia, chronic obstructive pulmonary disease, smoking, and use of positive airway pressure (PAP), decreased CRF alone (hazard ratio [HR]=1.91, 95% confidence interval [CI], 1.15 to 3.18; P=.01), but not SDB alone (HR=1.26, 95% CI, 0.75 to 2.13, P=.39) was associated with increased risk of MACE. Those with SDB and decreased CRF had greater risk of MACE compared with patients with decreased CRF alone (HR=1.85; 95% CI, 1.21 to 2.84; P<.005) after accounting for these confounders. The risk of MACE was attenuated in those with reduced CRF alone after additionally adjusting for adequate adherence to PAP (HR=1.59; 95% CI, 0.77 to 3.31; P=.21). CONCLUSION: The incidence of MACE, especially mortality, was high in this sample. Moderate-to-severe SDB with concurrent decreased CRF was associated with higher risk of MACE than decreased CRF alone. These results highlight the importance of possibly including CRF in the risk assessment of patients with SDB and, conversely, that of screening for SDB in patients with low peak VO2.

Fat Mass Index Better Identifies Metabolic Syndrome: Insights from Patients in Early Outpatient Cardiac Rehabilitation.

Body mass index (BMI) does not differentiate fat and lean mass or the distribution of adipose tissue. The purpose of this study was to examine the prevalence of metabolic syndrome (MetS) among patients entering outpatient cardiac rehabilitation (CR) across fat mass index (FMI) categories compared with BMI. This retrospective cross-sectional study evaluated dual-energy x-ray absorptiometry in 483 CR patients from 1 January 2014, through 31 December 2017. Clinical data were extracted from the electronic health record. Patients were grouped by FMI and BMI categories. Mean (SD) age of patients was 64.3 (14) years. The normal FMI category had 15 patients; excess fat, 74; and obese, 384. In contrast, 93, 174, and 216 were in the normal, overweight, and obese BMI categories, respectively. Prevalence of MetS was 0 (0%) in normal, 5 (1%) in excess fat, and 167 (54%) in obese FMI, with 97% in the obese category. MetS prevalence was 4 patients (0.8%) in normal, 39 (8%) in overweight, and 129 (27%) in obese BMI categories, with 75% of MetS in the obese category. FMI more accurately classified CR patients with metabolically abnormal fat (p < 0.001). FMI is a more sensitive index than BMI for metabolically abnormal fat of outpatient CR patients.

Added value of exercise test findings beyond traditional risk factors for cardiovascular risk stratification.

BACKGROUND: Functional aerobic capacity (FAC) determined by treadmill exercise testing (TMET) is associated with cardiovascular (CV) disease mortality independent of traditional CV risk factors and is a potentially underutilized tool. The purpose of this study was to determine added prognostic value of reduced FAC and other exercise test abnormalities beyond CV risk factors for predicting total and CV mortality. METHODS: The TMET database was queried for Minnesota patients (≥30 years) without baseline CV disease from September 21, 1993, through December 20, 2010. Risk factors and exercise abnormalities including low FAC (<80% predicted), abnormal heart rate recovery (<13 bpm), and abnormal electrocardiogram (ST depression ≥1 mm regardless of baseline) were extracted. Mortality data were obtained through February 2016. Patients were divided into 9 groups by abnormality number (0, 1, or ≥2) and risk factors (0, 1, or ≥2). Cox regression was used to determine mortality risk according to exercise abnormalities/CV risk factors, adjusted for age and sex. RESULTS: 19,551 patients met inclusion criteria; 1271 (6.5%) died over 12.4 ±â€¯5.0 years' follow-up (405 [32%] CV deaths). Exercise abnormalities significantly modified risk for every number of CV risk factors. Hazard ratios (95% CI) for total mortality (0 vs ≥2 abnormalities) were 2.4 (1.9-2.9; P < .001) for 0 CV risk factors; 2.7 (2.2-3.3; P < .001), 1 risk factor; and 6.1 (4.8-7.7; P < .001), ≥2 risk factors. Similar results were noted for CV disease mortality. CONCLUSIONS: Exercise test abnormalities strongly predict mortality beyond traditional CV risk factors. Our results indicate that TMET should be considered for CV risk assessment.