Impact of Interventricular Interaction on Ventricular Function: Insights From Right Ventricular Pressure-Volume Analysis.

BACKGROUND: Interventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle. OBJECTIVES: This study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests). METHODS: The investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients. RESULTS: With faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02). CONCLUSIONS: Interventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction.

Effect of patisiran on stroke volume in hereditary transthyretin-mediated amyloidosis: insights from pressure-volume analysis of the APOLLO study.

AIMS: Transthyretin-mediated (ATTR) amyloidosis is caused by deposition of transthyretin protein fibrils in the heart, nerves, and other organs. Patisiran, an RNA interference therapeutic that inhibits hepatic synthesis of transthyretin, was approved for the treatment of hereditary ATTR amyloidosis with polyneuropathy based on the phase 3 APOLLO study. We use left ventricular (LV) stroke volume (SV) to quantify LV function overtime and non-invasive pressure-volume techniques to delineate the effects of patisiran on LV mechanics in the pre-specified cardiac subpopulation of the APOLLO study. METHODS AND RESULTS: Left ventricular SV was assessed by transthoracic echocardiography at baseline, and after 9 and 18 months of therapy. To determine the mechanisms underlying changes in LV SV, non-invasive pressure-volume parameters, including the end-systolic and end-diastolic pressure-volume relationship, were derived using single beat techniques. At baseline, the mean SV was 51 ± 14 ml. At 9 months, the least-squares mean change in SV was -0.3 ± 1.2 ml for patisiran and -5.4 ± 1.9 ml for placebo (p = 0.021). At 18 months, the least-squares mean change in SV was -1.7 ± 1.3 ml for patisiran and - 8.1 ± 2.3 ml for placebo (p = 0.016). Decline in LV SV was driven by diminished LV capacitance in placebo relative to patisiran. CONCLUSIONS: Patisiran may delay progression of LV chamber dysfunction starting at 9 months of therapy. These data elucidate the mechanisms by which transthyretin-reducing therapies modulate progression of cardiac disease and need to be confirmed in ongoing phase 3 trials.

Insufficient Calorie Intake Worsens Post-Discharge Quality of Life and Increases Readmission Burden in Heart Failure.

OBJECTIVES: The purpose of this study was to evaluate the relationship between calorie intake and post-discharge outcomes in hospitalized patients with heart failure (HF). BACKGROUND: Malnutrition increases adverse outcomes in HF, and dietary sodium restriction may inadvertently worsen nutritional intake. METHODS: In a dietary intervention trial, baseline nutritional intake in HF inpatients was estimated using the Block Food Frequency Questionnaire (FFQ), and the Nutritional Risk Index (NRI) was calculated. Insufficient calorie intake was defined as <90% of metabolic needs, and a 15-point micronutrient deficiency score was created. Adjusted linear, logistic, and negative binomial regression were used to evaluate associations between insufficient calorie intake and quality of life (using the Kansas City Cardiomyopathy Questionnaire Clinical Summary [KCCQ-CS]), readmission risk, and days rehospitalized over 12 weeks. RESULTS: Among 57 participants (70 ± 8 years of age; 31% female; mean body mass index 32 ± 8 kg/m2); median sodium and calorie intake amounts were 2,987 mg/day (interquartile range [IQR]: 2,160 to 3,540 mg/day) and 1,602 kcal/day (IQR: 1,201 to 2,142 kcal/day), respectively; 11% of these patients were screened as malnourished by the NRI. All patients consuming <2,000 mg/day sodium had insufficient calorie intake; this group also more frequently had dietary micronutrient and protein deficiencies. At 12 weeks, patients with insufficient calorie intake had less improvement in the KCCQ-CS score (ß = -14.6; 95% confidence interval [CI]: -27.3 to -1.9), higher odds of readmission (odds ratio: 14.5; 95% CI: 2.2 to 94.4), and more days rehospitalized (incident rate ratio: 31.3; 95% CI: 4.3 to 229.3). CONCLUSIONS: Despite a high prevalence for obesity and rare overt malnutrition, insufficient calorie intake was associated with poorer post-discharge quality of life and increased burden of readmission in patients with HF. Inpatient dietary assessment could improve readmission risk stratification and identify patients for nutritional intervention. (Geriatric Out of Hospital Randomized Meal Trial in Heart Failure [GOURMET-HF] NCT02148679).

Pathophysiology and Advanced Hemodynamic Assessment of Cardiogenic Shock.

Cardiogenic shock (CGS) is common and highly morbid. According to the National Inpatient Sample, there are more than 100,000 cases per year, and 30-day mortality approaches 50% despite improvements in critical care practices and novel mechanical therapies targeted at restoring normal hemodynamics. This issue aims to enhance clinicians' understanding of CGS, and this review specifically focuses on the underlying pathophysiology. We examine the definition and etiologies of CGS, approaches to risk assessment, and the pressure-volume loop framework that is the foundation for conceptualizing ventricular mechanics, ventricular-vascular interactions, and the derangements observed in CGS. This overview will also contextualize subsequent chapters that discuss nuances of CGS encountered in particular scenarios (ie, post-myocardial infraction, acutely decompensated chronic heart failure, post-cardiac surgery), address pharmacological and mechanical treatments for CGS, and review CGS in a case-based format.

Low-sodium dietary approaches to stop hypertension diet reduces blood pressure, arterial stiffness, and oxidative stress in hypertensive heart failure with preserved ejection fraction.

Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In salt-sensitive HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155-138 mm Hg; P=0.02) and diastolic blood pressure (79-72 mm Hg; P=0.04), 24-hour ambulatory systolic (130-123 mm Hg; P=0.02) and diastolic blood pressure (67-62 mm Hg; P=0.02), and carotid-femoral pulse wave velocity (12.4-11.0 m/s; P=0.03). Urinary F2-isoprostanes decreased by 31% (209-144 pmol/mmol Cr; P=0.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of salt-sensitive hypertension, a phenotype present in many HFPEF animal models and suggest shared pathophysiological mechanisms linking these 2 conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF.