Rationale for a New Low-Dose Triple Single Pill Combination for the Treatment of Hypertension.

Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these 'hypertension polypills' were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.

The effect of salt substitution on frequency and severity of headache: results from the SSaSS cluster-randomised controlled trial of 20,995 participants.

BACKGROUND: Headache is one of the most common neurological symptoms. Headache disorders are associated with a high global burden of disease. Prior studies indicate that short-to-medium term sodium reduction reduces headache symptom. This study evaluated the effects of long-term reduced-sodium, added-potassium salt on headache frequency and severity in rural China. METHODS: The Salt substitute and stroke study (SSaSS) was an open-label cluster-randomised trial in rural China designed to evaluate the effect of salt substitution on mortality and cardiovascular events. Participants included adults with a history of prior stroke and those aged ≥60 years with uncontrolled high blood pressure (BP). Villages were randomly assigned in a 1:1 ratio either to intervention with salt substitute (75% sodium chloride and 25% potassium chloride by mass) or to control with continued use of regular salt (100% sodium chloride). In this pre-specified analysis, between-group differences in headache frequency and severity were evaluated. The study was registered with ClinicalTrials.gov (identifier number: NCT02092090). RESULTS: A total of 20,995 participants were included in the trial (mean age 64.3 years, 51% female, mean follow-up 4.7 years). At final follow-up at the end of the study, headache outcome data including frequency and severity of headaches was available for 16,486 (98%) of 16,823 living participants. Overall, 4454/16,486 (27%) individuals reported having headache: 27.4% in the intervention group (2301/8386) vs 26.6% in the control group (2153/8100) (RR 1.04, 95% CI: 0.93, 1.16, p = 0.48). There was no difference in headache severity between intervention and control groups (p = 0.90). CONCLUSION: Long term salt substitution did not reduce the frequency or severity of headaches in this population.

Transforming blood pressure control in primary care through a novel remote decision support strategy based on wearable blood pressure monitoring: The NEXTGEN-BP randomized trial protocol.

BACKGROUND: Despite high blood pressure being the leading preventable risk factor for death, only 1 in 3 patients achieve target blood pressure control. Key contributors to this problem are clinical inertia and uncertainties in relying on clinic blood pressure measurements to make treatment decisions. METHODS: The NEXTGEN-BP open-label, multicenter, randomized controlled trial will investigate the efficacy, safety, acceptability and cost-effectiveness of a wearable blood pressure monitor-based care strategy for the treatment of hypertension, compared to usual care, in lowering clinic blood pressure over 12 months. NEXTGEN-BP will enroll 600 adults with high blood pressure, treated with 0 to 2 antihypertensive medications. Participants attending primary care practices in Australia will be randomized 1:1 to the intervention of a wearable-based remote care strategy or to usual care. Participants in the intervention arm will undergo continuous blood pressure monitoring using a wrist-wearable cuffless device (Aktiia, Switzerland) and participate in 2 telehealth consultations with their primary care practitioner (general practitioner [GP]) at months 1 and 2. Antihypertensive medication will be up-titrated by the primary care practitioner at the time of telehealth consults should the percentage of daytime blood pressure at target over the past week be <90%, if clinically tolerated. Participants in the usual care arm will have primary care consultations according to usual practice. The primary outcome is the difference between intervention and control in change in clinic systolic blood pressure from baseline to 12 months. Secondary outcomes will be assessed at month 3 and month 12, and include acceptability to patients and practitioners, cost-effectiveness, safety, medication adherence and patient engagement. CONCLUSIONS: NEXTGEN-BP will provide evidence for the effectiveness and safety of a new paradigm of wearable cuffless monitoring in the management of high blood pressure in primary care. TRIAL REGISTRATION: ACTRN12622001583730.

Evaluation of the ability of a commercially available cuffless wearable device to track blood pressure changes.

OBJECTIVES: Cuffless wearable blood pressure (BP) devices may allow detailed evaluation of BP for prolonged periods, but their ability to accurately track BP changes is uncertain. We investigated whether a commercially available cuffless wearable device tracks: 24-h systolic (SBP) and diastolic BP (DBP) compared to conventional ambulatory monitoring (ABPM); and antihypertensive medication-induced BP changes compared to cuff-based home BP monitoring (HBPM). METHODS: We fitted 41 participants (32% females, 58 ±â€Š14 years, 80% hypertensive) with a wrist-wearable cuffless BP device (Aktiia) continuously for 6-12 days. At the beginning and the end of this period, 24-h ABPM was performed. Three participants with hypertension (one female; 60 ±â€Š8 years) wore the Aktiia device and performed HBPM continuously one week before and 2 weeks after antihypertensive medication uptitration. RESULTS: Compared to ABPM, Aktiia reported higher average SBP for 24-h (difference 4.9 mmHg, 95% CI [1.9, 7.9]) and night-time (15.5[11.8, 19.1] mmHg; all P ≤ 0.01), but similar daytime (1.0 [-1.8, 3.8] mmHg; P = 0.48). Similarly, average cuffless DBP was higher for 24-h (4.2 [2.3, 6.0] mmHg) and night-time (11.8 [9.5, 14.1] mmHg; both P  < 0.001), but similar during daytime (1.4 [-0.4, 3.23] mmHg; P  = 0.13). Aktiia also reported reduced night-time dip for SBP (difference 14.2 [12.1, 16.3] mmHg) and DBP (10.2 [8.5, 11.9] mmHg; both P  < 0.001). The average medication-induced SBP/DBP decline after 2 weeks of uptitration was -1.0/-0.8 mmHg with Aktiia vs. -19.7/-11.5 mmHg with HBPM ( P  = 0.03 for difference). CONCLUSION: This cuffless wearable device did not accurately track night-time BP decline and results suggested it was unable to track medication-induced BP changes.

Reduced efficacy of blood pressure lowering drugs in the presence of diabetes mellitus-results from the TRIUMPH randomised controlled trial.

We investigated whether diabetes mellitus (DM) affects the efficacy of a low-dose triple combination pill and usual care among people with mild-moderate hypertension. TRIUMPH (TRIple pill vs Usual care Management for Patients with mild-to-moderate Hypertension) was a randomised controlled open-label trial of patients requiring initiation or escalation of antihypertensive therapy. Patients were randomised to a once-daily low-dose triple combination polypill (telmisartan-20mg/amlodipine-2.5 mg/chlorthalidone-12.5 mg) or usual care. This analysis compared BP reduction in people with and without DM, both in the intervention and control groups over 24-week follow-up. Predicted efficacy of prescribed therapy was calculated (estimation methods of Law et al.). The trial randomised 700 patients (56 ± 11 yrs, 31% DM). There was no difference in the number of drugs prescribed or predicted efficacy of therapy between people with DM and without DM. However, the observed BP reduction from baseline to week 24 was lower in those with DM compared to non-diabetics in both the triple pill (25/11 vs 31/15 mmHg, p ≤ 0.01) and usual care (17/7 vs 22/11 mmHg, p ≤ 0.01) groups, and these differences remained after multivariable adjustment. DM was a negative predictor of change in BP (ß-coefficient -0.08, p = 0.02). In conclusion, patients with DM experienced reduced efficacy of BP lowering therapies as compared to patients without DM, irrespective of the type of BP lowering therapy received.

COVID-19 mRNA vaccines and myopericarditis.

Globally, vaccination against COVID-19 has prevented countless infections, hospitalisations and death and represents the most successful intervention in combating the pandemic caused by SARS-CoV-2 infection. Utilisation of existing mRNA vaccine technology has allowed for rapid development of highly immunogenic and effective vaccines. Myopericarditis can occur as an adverse effect of COVID-19 mRNA vaccination, albeit at significantly lower rates than those that occur during SARS-CoV-2 infection. Higher rates are seen in adolescent males, usually within 1-5 days of receiving the second vaccine dose. Although most cases are self-limited and respond to first-line treatment, refractory cases can occur, with a limited evidence base on which to guide management. Here, we present a brief review of COVID-19 mRNA vaccines and associated myopericarditis including risk factors, proposed mechanism, and treatment including management strategies for refractory disease.

Frontiers of cardiovascular polypills: From atherosclerosis and beyond.

Fixed-dose combination (FDC) therapies (also known as polypills) remain underutilized in clinical practice despite over two decades of evidence from randomized controlled trials demonstrating increased adherence to multidrug therapy, improved cardiovascular disease (CVD) risk factor control, and lower incidence of cardiovascular events. Evidence demonstrates that FDC-based implementation strategies can substantially complement and augment current strategies for CVD risk prevention globally. The next decade is likely to extend the frontier of cardiovascular FDC therapies, particularly given expected advances in FDC manufacturing technology and accessibility. FDC-based anti-hypertensive therapies are emerging as integral components of a pragmatic blood pressure lowering strategy. Cardiovascular FDCs are rapidly approaching its coming of age, transforming from heavily hyped research tools to pragmatic clinical instruments. This review evaluates the current evidence for cardiovascular FDCs, barriers to current use, and potential next generation advances.

Do bisphosphonates and RANKL inhibitors alter the progression of coronary artery calcification? A systematic review and meta-analysis protocol.

INTRODUCTION: Whether bisphosphonates and RANKL inhibitors play a novel role in delaying cardiovascular calcification is unknown. Their action on regulatory enzymes in the mevalonic acid pathway, which is implicated in both bone and lipid metabolism, may be a novel therapeutic target to manage coronary artery disease (CAD). Such therapies may particularly be relevant in those for whom traditional cardiovascular therapies are no longer sufficient to control disease progression. METHODS AND ANALYSIS: We will perform a systematic review which aims to synthesise evidence regarding whether use of bisphosphonates or use of the RANKL inhibitor denosumab delays coronary artery calcium (CAC) progression. Eligible studies will include longitudinal studies investigating CAC progression in patients aged >18 years taking either a bisphosphonate or denosumab compared with those who do not. Embase, MEDLINE and Cochrane will be searched using prespecified search terms. Studies will be screened by title and abstract independently and then in full to determine suitability for inclusion in the review. Extracted data will include that relating to study and participant characteristics. The primary outcome will be the CAC score. Secondary outcomes will include aortic and carotid artery calcification. Meta-analysis will be performed if sufficient data are available. ETHICS AND DISSEMINATION: This study does not require ethics as it is a systematic review of the literature. The results of the review described within this protocol will be distributed via presentations at relevant conferences and publication within a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: The systematic review pertaining to this protocol is registered with PROSPERO (Registration ID: CRD42022312377).

Renin-Angiotensin System Inhibitors in Patients With COVID-19: A Meta-Analysis of Randomized Controlled Trials Led by the International Society of Hypertension.

Background Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. Methods and Results MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69-1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33-1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05-3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. Conclusions This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19.

Identification of a Distinct Platelet Phenotype in the Elderly: ADP Hypersensitivity Coexists With Platelet PAR (Protease-Activated Receptor)-1 and PAR-4-Mediated Thrombin Resistance.

BACKGROUND: Thrombin (via PAR [protease-activated receptor]-1 and PAR-4) and ADP (via P2Y12 receptors) are potent endogenous platelet activators implicated in the development of cardiovascular disease. We aimed to assess whether platelet pathways alter with aging. METHODS: We characterized platelet activity in community-dwelling volunteers (n=174) in the following age groups: (1) 20 to 30 (young); (2) 40 to 55 (middle-aged); (3) ≥70 years (elderly). Platelet activity was assessed by aggregometry; flow cytometry (surface markers [P-selectin: alpha granule release, CD63: dense granule release, PAC-1: measure of conformationally active GPIIb/IIIa at the fibrinogen binding site]) measured under basal conditions and after agonist stimulation [ADP, thrombin, PAR-1 agonist or PAR-4 agonist]); receptor cleavage and quantification; fluorometry; calcium flux; ELISA. RESULTS: The elderly had higher basal platelet activation than the young, evidenced by increased expression of P-selectin, CD63, and PAC-1, which correlated with increasing inflammation (IL [interleukin]-1ß/IL-6). The elderly demonstrated higher P2Y12 receptor density, with greater ADP-induced platelet aggregation (P<0.05). However, elderly subjects were resistant to thrombin, achieving less activation in response to thrombin (higher EC50) and to selective stimulation of both PAR-1 and PAR-4, with higher basal PAR-1/PAR-4 cleavage and less inducible PAR-1/PAR-4 cleavage (all P<0.05). Thrombin resistance was attributable to a combination of reduced thrombin orienting receptor GPIbα (glycoprotein Ibα), reduced secondary ADP contribution to thrombin-mediated activation, and blunted calcium flux. D-Dimer, a marker of in situ thrombin generation, correlated with platelet activation in the circulation, ex vivo thrombin resistance, and circulating inflammatory mediators (TNF [tumor necrosis factor]-α/IL-6). CONCLUSIONS: Aging is associated with a distinctive platelet phenotype of increased basal activation, ADP hyperreactivity, and thrombin resistance. In situ thrombin generation associated with systemic inflammation may be novel target to prevent cardiovascular disease in the elderly.

Association of Low-Dose Triple Combination Therapy vs Usual Care With Time at Target Blood Pressure: A Secondary Analysis of the TRIUMPH Randomized Clinical Trial.

Importance: Cumulative exposure to high blood pressure (BP) is an adverse prognostic marker. Assessments of BP control over time, such as time at target, have been developed but assessments of the effects of BP-lowering interventions on such measures are lacking. Objective: To evaluate whether low-dose triple combination antihypertensive therapy was associated with greater rates of time at target compared with usual care. Design, Setting, and Participants: The Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) trial was a open-label randomized clinical trial of low-dose triple BP therapy vs usual care conducted in urban hospital clinics in Sri Lanka from February 2016 to May 2017. Adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg or in patients with diabetes or chronic kidney disease, systolic BP >130 mm Hg and/or diastolic BP >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy were included. Patients were excluded if they were currently taking 2 or more blood pressure-lowering drugs or had severe or uncontrolled blood pressure, accelerated hypertension or physician-determined need for slower titration of treatment, a contraindication to the triple combination pill therapy, an unstable medical condition, or clinically significant laboratory values deemed by researchers to be unsuitable for the study. All 700 individuals in the original trial were included in the secondary analysis. This post hoc analysis was conducted from December 2020 to December 2021. Intervention: Once-daily fixed-dose triple combination pill (telmisartan 20 mg, amlodipine 2.5 mg, and chlorthalidone 12.5 mg) therapy vs usual care. Main Outcomes and Measures: Between-group differences in time at target were compared over 24 weeks of follow-up, with time at target defined as percentage of time at target BP. Results: There were a total of 700 randomized patients (mean [SD] age, 56 [11] years; 403 [57.6%] women). Patients allocated to the triple pill group (n = 349) had higher time at target compared with those in the usual care group (n = 351) over 24 weeks' follow-up (64% vs 43%; risk difference, 21%; 95% CI, 16-26; P < .001). Almost twice as many patients receiving triple pill therapy achieved more than 50% time at target during follow-up (64% vs 37%; P < .001). The association of the triple pill with an increase in time at target was seen early, with most patients achieving more than 50% time at target by 12 weeks. Those receiving the triple pill achieved a consistently higher time at target at all follow-up periods compared with those receiving usual care (mean [SD]: 0-6 weeks, 36.3% [30.9%] vs 21.7% [28.9%]; P < .001; 6-12 weeks, 55.2% [31.9%] vs 33.7% [33.0%]; P < .001; 12-24 weeks, 66.0% [31.1%] vs 43.5% [34.3%]; P < .001). Conclusions and Relevance: To our knowledge, this analysis provides the first estimate of time at target as an outcome assessing longitudinal BP control in a randomized clinical trial. Among patients with mild to moderate hypertension, treatment with a low-dose triple combination pill was associated with substantially higher time at target compared with usual care.

Hemoglobin, Frailty, and Long-term Cardiovascular Events in Community-Dwelling Older Men Aged ≥ 70 Years.

BACKGROUND: Anemia is associated with increased risk of all-cause mortality in older populations. However, the relationship between hemoglobin and major adverse cardiovascular events (MACE), and whether this is modulated by frailty, is unclear. METHODS: CHAMP (Concord Health and Ageing in Men Project) is a prospective study of community-dwelling men aged ≥ 70 years. The relationship between hemoglobin and 7-year MACE was analysed by means of Cox regression. The Youden index was used to determine the optimal hemoglobin cutoff point in predicting MACE. Frailty was assessed with the use of the Fried criteria. RESULTS: The cohort comprised 1604 men (mean ± SD age 76.9 ± 5.5 years). Decreasing hemoglobin was associated with increased comorbidity, frailty, and MACE (P < 0.001), with 140 g/L the optimal cutoff point for predicting MACE. Hemoglobin, age, and frailty independently predicted MACE (all P < 0.001). Each 10 g/L decrement in hemoglobin level was associated with increased risk of MACE (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.06-1.20; P < 0.001), all-cause mortality (HR 1.20, 95% CI 1.12-1.29; P < 0.001), cardiovascular mortality (HR 1.07, 95% CI 1.01-1.14; P = 0.025), myocardial infarction (HR 1.17, 95% CI 1.09-1.25; P < 0.001), and heart failure (HR 1.17, 95% CI 1.09-1.25; P < 0.001). When stratified into hemoglobin quintiles, men in the lowest 2 quintiles (Hb 133-140 g/L and < 132g/L, respectively) were at increased risk of MACE, cardiovascular mortality, myocardial infarction, and heart failure (all P < 0.05). This relationship for MACE was independent from frailty status, with the test for interaction between frailty and hemoglobin not reaching significance (P = 0.24). CONCLUSIONS: Low hemoglobin was associated with increased MACE in community-dwelling older men independently from frailty. A hemoglobin cutoff point of 140 g/L, a level that is above contemporary definitions of anemia, predicted long-term MACE.

Perspective: Collagen induced platelet activation via the GPVI receptor as a primary target of colchicine in cardiovascular disease.

Colchicine has been demonstrated to reduce cardiovascular death, myocardial infarction (MI), ischemic stroke, and ischemia-driven coronary revascularization in people with coronary artery disease (CAD). These reductions were observed even in patients already taking antiplatelet therapy. As well as having anti-inflammatory effects, colchicine demonstrates antiplatelet effects. We propose that colchicine's antiplatelet effects primarily target collagen-induced platelet activation via the collagen receptor, glycoprotein (GP)VI, which is critical for arterial thrombosis formation. In settings such as stroke and MI, GPVI signaling is upregulated. We have demonstrated in vitro that therapeutic concentrations of colchicine lead to a decrease in collagen-induced platelet aggregation and alter GPVI signaling. Clinical studies of colchicine given for 6 months lead to a significant reduction in serum GPVI levels in CAD patients, which may ameliorate thrombotic risk. Future evaluation of the effects of colchicine in clinical trials should include assessment of its effects on collagen-mediated platelet activation, and consideration be given to quantifying the contribution of such antiplatelet effects additional to the known anti-inflammatory effects of colchicine.

Chronic occlusion of the thoracic aorta: a novel cause of pleuropericardial effusions and pancytopenia.

A 57-year-old man had presented with a 6-month history of worsening dyspnea, renal failure, hypertension, pancytopenia, and a continuous machinery murmur. Imaging studies revealed pleuropericardial effusions that recurred despite aspiration and suprarenal mid-thoracic aortic occlusion (AO) with extensive collateral vessels to the chest wall, rectus sheath, and diaphragm. A right axillofemoral bypass transformed his clinical course. The murmurs, renal failure, pleuropericardial drainage, and pancytopenia resolved, and his hypertension had markedly improved. The association of chronic AO with pleuropericardial effusions without peripheral edema or ascites was most likely due to increased supradiaphragmatic interstitial pressure, and the bone marrow hypoperfusion likely explains the pancytopenia. In addition to posing diagnostic challenges, chronic AO reveals unique insights into the pathogenesis of pleuropericardial effusions and pancytopenia.

Long-term prognostic utility of computed tomography coronary angiography in older populations.

AIMS: The long-term prognostic value of coronary computed tomography angiography (CCTA)-identified coronary artery disease (CAD) has not been evaluated in elderly patients (≥70 years). We compared the ability of coronary CCTA to predict 5-year mortality in older vs. younger populations. METHODS AND RESULTS: From the prospective CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, we analysed CCTA results according to age <70 years (n = 7198) vs. ≥70 years (n = 1786). The severity of CAD was classified according to: (i) maximal stenosis degree per vessel: none, non-obstructive (1-49%), or obstructive (>50%); (ii) segment involvement score (SIS): number of segments with plaque. Cox-proportional hazard models assessed the relationship between CCTA findings and time to mortality. At a mean 5.6 ± 1.1 year follow-up, CCTA-identified CAD predicted increased mortality compared with patients with a normal CCTA in both <70 years [non-obstructive hazard ratio (HR) confidence interval (CI): 1.70 (1.19-2.41); one-vessel: 1.65 (1.03-2.67); two-vessel: 2.24 (1.21-4.15); three-vessel/left main: 4.12 (2.27-7.46), P < 0.001] and ≥70 years [non-obstructive: 1.84 (1.15-2.95); one-vessel: HR (CI): 2.28 (1.37-3.81); two-vessel: 2.36 (1.33-4.19); three-vessel/left main: 2.41 (1.33-4.36), P = 0.014]. Similarly, SIS was predictive of mortality in both <70 years [SIS 1-3: 1.57 (1.10-2.24); SIS ≥4: 2.42 (1.65-3.57), P < 0.001] and ≥70 years [SIS 1-3: 1.73 (1.07-2.79); SIS ≥4: 2.45 (1.52-3.93), P < 0.001]. CCTA findings similarly predicted long-term major adverse cardiovascular outcomes (MACE) (all-cause mortality, myocardial infarction, and late revascularization) in both groups compared with patients with no CAD. CONCLUSION: The presence and extent of CAD is a meaningful stratifier of long-term mortality and MACE in patients aged <70 years and ≥70 years old. The presence of obstructive and non-obstructive disease and the burden of atherosclerosis determined by SIS remain important predictors of prognosis in older populations.

Feeding Induces Left Atrial Compression and Impedes Cardiac Filling in Patients With Large Hiatal Hernia.

BACKGROUND: Patients with large hiatal hernias (HH) frequently experience postprandial dyspnea. The aim of this study was to evaluate whether feeding induced cardiac compression in these patients using echocardiography. METHODS: Transthoracic echocardiography was performed during fasting and 30 min after feeding (300 g rice pudding) in patients with HHs (n = 32; mean age, 72 ± 9 years). A subset of patients (n = 15; mean age, 76 ± 6 years) were evaluated postoperatively. RESULTS: Preoperatively, feeding decreased left atrial (LA) volumes (maximal 27.4 ± 11.3 vs 19.2 ± 9.7 mL/m2, P < .001; minimal 13.1 ± 7.0 vs 6.9 ± 5.1 mL/m2, P < .001), and increased LA inflow velocities (systolic wave 0.62 ± 0.14 vs 0.77 ± 0.17 m/sec, P < .01; diastolic wave 0.46 ± 0.13 vs 0.59 ± 0.13 m/sec, P < .01), mitral inflow velocities (E wave 0.79 ± 0.17 vs 0.94 ± 0.19 m/sec, P < .01; A wave 0.93 ± 0.20 vs 1.05 ± 0.22 m/sec, P < .01), and E/E' ratio (12.1 ± 2.7 vs 13.7 ± 3.9, P < .01). Cardiac output (6.3 ± 1.6 vs 7.24 ± 2.0 L, P < .01) increased postprandially by marked heart rate augmentation (68.8 ± 7.0 vs 84.2 ± 8.4 beats/min, P < .01), with modest stroke volume increase (88.5 ± 16.7 vs 94.3 ± 19.5 mL, P = .03). After HH surgery, feeding did not change LA volumes (maximal 52.9 ± 13.6 vs 53.4 ± 12.5 mL, P = .89; minimal 28.6 ± 12.2 vs 27.4 ± 8.7 mL, P = .59) or E/E' ratio (10.9 ± 2.1 vs 11.3 ± 2.3) and induced more modest alterations in LA inflow (systolic wave 0.58 ± 0.17 vs 0.68 ± 0.16 m/sec, P = .01; diastolic wave 0.41 ± 0.12 vs 0.47 ± 0.13 m/sec, P = .01) and mitral inflow (E wave 0.69 ± 0.15 vs 0.80 ± 0.13 m/sec, P < .01; A wave 0.92 ± 0.13 vs 1.01 ± 0.18 m/sec, P = .02). Postoperatively, feeding increased cardiac output by substantial stroke volume augmentation (81.9 ± 16.5 vs 90.8 ± 16.0 mL, P = .01), with only modest increase in heart rate (69.8 ± 9.1 vs 75.9 ± 10.5 beats/min, P < .01). CONCLUSIONS: Feeding produces marked LA compression in patients with HHs, inducing compensatory exaggerated responses in cardiac inflow and hemodynamic status. These compensatory mechanisms improve postoperatively following resolution of LA compression, likely explaining the debility noted preoperatively.