This study aimed to define the influence of healthy aging on the central hemodynamic response to exercise. Advancing age results in numerous alterations to the cardiovascular system and is a major ...risk factor to develop heart failure. In patients with suspected heart failure with preserved ejection fraction, there is an increasing interest in the incorporation of stress hemodynamic studies into the diagnostic evaluation pathway. However, many patients with suspected heart failure with preserved ejection fraction are older, and there are few data regarding the effect of aging on the normal central hemodynamic responses to exercise. Therefore, we examined 55 healthy patients using right-sided cardiac catheterization with exercise. Mean age was 49.6 years, with 36% older than 55 years. On exercise, the mean pulmonary artery pressure was higher with advancing age (r = 0.412, p = 0.002). Additionally, age was negatively associated with cardiac index (r = 0.407, p = 0.005). The exercise-induced rise in pulmonary capillary wedge pressure (r = 0.378, p = 0.004) was greater with advancing age. Pulse pressure measured during exercise (r = 0.541, p <0.01) increased with age, as did diastolic dysfunction assessed by E/A ratio (r = 0.569, p <0.001). In conclusion, aging was associated with decreased cardiac output and increased pulmonary artery pressure during exercise, which developed as the consequence of both increased pulmonary vasculature resistance and higher left ventricular filling pressures.
The ratio of tricuspid regurgitation velocity (TRV) to the time-velocity integral of the right ventricular outflow tract (TVIRVOT) has been studied as a reliable measure to distinguish elevated from ...normal pulmonary vascular resistance (PVR). The equation TRV/TVIRVOT × 10 + 0.16 (PVRecho) has been shown to provide a good noninvasive estimate of PVR. However, its role in patients with significantly elevated PVR (> 6 Wood units WU) has not been conclusively evaluated. The aim of this study was to establish the validity of the TRV/TVIRVOT ratio as a correlate of PVR. The role of TRV/TVIRVOT was also compared with that of a new ratio, TRV(2)/TVIRVOT, in patients with markedly elevated PVR (>6 WU).
Data from five validation studies using TRV/TVIRVOT as an estimate of PVR were compared with invasive PVR measurements (PVRcath). Multiple linear regression analyses were generated between PVRcath and both TRV/TVIRVOT and TRV(2)/TVIRVOT. Both PVRecho and a new derived regression equation based on TRV(2)/TVIRVOT: 5.19 × TRV(2)/TVIRVOT - 0.4 (PVRecho2) were compared with PVRcath using Bland-Altman analysis. Logistic models were generated, and cutoff values for both TRV/TVIRVOT and TRV(2)/TVIRVOT were obtained to predict PVR > 6 WU.
One hundred fifty patients remained in the final analysis. Linear regression analysis between PVRcath and TRV/TVIRVOT revealed a good correlation (r = 0.76, P < .0001, Z = 0.92). There was a better correlation between PVRcath and TRV(2)/TVIRVOT (r = 0.79, P < .0001, Z = -0.01) in the entire cohort as well as in patients with PVR > 6 WU. Moreover, PVRecho2 compared better with PVRcath than PVRecho using Bland-Altman analysis in the entire cohort and in patients with PVR > 6 WU. TRV(2)/TVIRVOT and TRV/TVIRVOT both predicted PVR > 6 WU with good sensitivity and specificity.
TRV/TVIRVOT is a reliable method to identify patients with elevated PVR. In patients with TRV/TVIRVOT > 0.275, PVR is likely > 6 WU, and PVRecho2 derived from TRV(2)/TVIRVOT provides an improved noninvasive estimate of PVR compared with PVRecho.
Abstract Objective Heart failure with preserved ejection fraction (HFpEF) is characterized by elevated left atrial pressure during rest and/or exercise. The Reduce LAP-HF (Reduce Elevated Left Atrial ...Pressure in Patients With Heart Failure) trial will evaluate the safety and performance of the Interatrial Shunt Device (IASD) System II, designed to directly reduce elevated left atrial pressure, in patients with HFpEF. Methods The Reduce LAP-HF Trial is a prospective, nonrandomized, open-label trial to evaluate a novel device that creates a small permanent shunt at the level of the atria. A minimum of 60 patients with ejection fraction ≥40% and New York Heart Association functional class III or IV heart failure with a pulmonary capillary wedge pressure (PCWP) ≥15 mm Hg at rest or ≥25 mm Hg during supine bike exercise will be implanted with an IASD System II, and followed for 6 months to assess the primary and secondary end points. Safety and standard clinical follow-up will continue through 3 years after implantation. Primary outcome measures for safety are periprocedural and 6-month major adverse cardiac and cerebrovascular events (MACCE) and systemic embolic events (excluding pulmonary thromboembolism). MACCE include death, stroke, myocardial infarction, or requirement of implant removal. Primary outcome measures for device performance include success of device implantation, reduction of PCWP at rest and during exercise, and demonstration of left-to-right flow through the device. Key secondary end points include exercise tolerance, quality of life, and the incidence of heart failure hospitalization. Conclusion Reduce LAP-HF is the first trial intended to lower left atrial pressure in HFpEF by means of creating a permanent shunt through the atrial septum with the use of a device. Although the trial is primarily designed to study safety and device performance, we also test the pathophysiologic hypothesis that reduction of left atrial pressure will improve symptoms and quality of life in patients with HFpEF.
Abstract Background A treatment based on an interatrial shunt device has been proposed for counteracting elevated pulmonary capillary wedge pressure (PCWP) in patients with heart failure and mildly ...reduced or preserved ejection fraction (HFpEF). We tested the theoretical hemodynamic effects of this approach with the use of a previously validated cardiovascular simulation. Methods and Results Rest and exercise hemodynamics data from 2 previous independent studies of patients with HFpEF were simulated. The theoretical effects of a shunt between the right and left atria (diameter up to 12 mm) were determined. The interatrial shunt lowered PCWP by ∼3 mm Hg under simulated resting conditions (from 10 to 7 mm Hg) and by ∼11 mm Hg under simulated peak exercise conditions (from 28 to 17 mm Hg). Left ventricular cardiac output decreased ∼0.5 L/min at rest and ∼1.3 L/min at peak exercise, with corresponding increases in right ventricular cardiac output. However, because of the reductions in PCWP, right atrial and pulmonary artery pressures did not increase. A majority of these effects were achieved with a shunt diameter of 8–9 mm. The direction of flow though the shunt was left to right in all of the conditions tested. Conclusions The interatrial shunt reduced left-sided cardiac output with a marked reduction in PCWP. This approach may reduce the propensity for heart failure exacerbations and allow patients to exercise longer, thus attaining higher heart rates and cardiac outputs with the shunt compared with no shunt. These results support clinical investigation of this approach and point out key factors necessary to evaluate its safety and hemodynamic effectiveness.
To the Editor: Acute renal injury after exposure to radiographic contrast media, contrast-induced nephropathy (CIN), accounts for a substantial proportion of all cases of acute renal failure (1). ......in patients undergoing coronary intervention, it is increasingly evident that the development of CIN is accompanied by higher periprocedural mortality, longer hospitalization, and a higher likelihood of complications (3).
Patients with HFPEF (n = 20; age: 68 ± 2 years; left ventricular ejection fraction 64 ± 2%) underwent right heart catheterization and radial arterial cannulation for measurement of hemodynamics at ...rest and during peak symptom-limited exercise, as described previously (3). Pretreatment exercise hemodynamic responses (presented as delta values for pre-placebo vs. pre-milrinone) were generally not significantly different: heart rate (28 ± 5 vs. 30 ± 3 beats/min), mean arterial pressure (21 ± 4 vs. 22 ± 3 mm Hg), mean pulmonary artery pressure (17 ± 2 vs. 23 ± 2 mm Hg), cardiac index (1.8 ± 0.2 vs. 2.3 ± 0.2 l/min/m2), and stroke volume index (6 ± 1 vs. 4 ± 1 ml/m2).
Percutaneous Cardiac Recirculation-Mediated Gene Transfer of an Inhibitory Phospholamban Peptide Reverses Advanced Heart Failure in Large Animals David M. Kaye, Arthur Preovolos, Tanneale Marshall, ...Melissa Byrne, Masahiko Hoshijima, Roger Hajjar, Justin A. Mariani, Salvatore Pepe, Kenneth R. Chien, John M. Power The successful clinical translation of gene and cell therapy for heart failure (HF) is currently limited by the lack of safe, efficient, and selective delivery systems. We developed a novel percutaneous closed-loop recirculatory system for gene transfer in the large animal heart. In pacing-induced HF, delivery of an adenovirus expressing a pseudophosphorylated mutant of phospholamban (AdS16EPLN) significantly reversed HF progression. Hemodynamic improvements were also accompanied by significant improvement in the expression of phospholamban and Ca2+ -ATPase activity. This study documents the successful deployment of a novel closed-loop system for cardiac gene therapy in experimental HF.
Platelet-rich plasma (PRP) has the potential to regenerate tissues and decrease pain through the effects of bioactive molecules and growth factors present in alpha granules. Several PRP preparation ...systems are available with varying end products, doses of growth factors, and bioactive molecules. This article presents the biology of PRP, the preparation of PRP, and the effects PRP-related growth factors have on tissue healing and repair. Based on available evidence-based literature, the success of PRP therapy depends on the method of preparation and composition of PRP, the patient's medical condition, anatomic location of the injection, and the type of tissue injected.
Objectives The purpose of this study was to invasively investigate the hemodynamic response to exercise in patients with heart failure with normal ejection fraction (HFNEF) and to evaluate the ...ability of the peak early diastolic transmitral velocity to peak early diastolic annular velocity ratio (E/e′) to reflect exercise hemodynamics. Background There is little information regarding the hemodynamic response to exercise in HFNEF. Methods Patients with HFNEF (n = 14) and asymptomatic controls (n = 8) underwent right-side heart catheterization at rest and during supine cycle ergometer exercise and echocardiography with measurement of resting and peak exercise E/e′. Results Resting pulmonary capillary wedge pressure (PCWP) (10 ± 4 mm Hg vs. 10 ± 4 mm Hg; p = 0.94) was similar in HFNEF patients and controls, but stroke volume index (SVI) (p = 0.02) was lower, and systemic vascular resistance index (SVRI) (p = 0.01) was higher in patients. Patients stopped exercise at lower work rate (0.63 ± 0.29 W/kg vs. 1.13 ± 0.49 W/kg; p = 0.006). Although peak exercise PCWP was similar in both groups (23 ± 6 mm Hg vs. 20 ± 7 mm Hg; p = 0.31), the peak PCWP/work rate ratio was higher in patients compared with controls (46 ± 31 mm Hg/W/kg vs. 20 ± 9 mm Hg/W/kg; p = 0.03). Peak exercise SVI (p = 0.001) was lower and SVRI was higher (p = 0.01) in patients. Resting E/e′ was modestly elevated in patients (13.2 ± 4.1 vs. 9.5 ± 3.4; p = 0.04). Peak exercise E/e′ did not differ between the groups (11.1 ± 3.4 vs. 9.4 ± 3.4; p = 0.28). Conclusions The HFNEF patients achieved a similar peak exercise PCWP to that of asymptomatic controls, at a much lower workload. This occurs at a lower SVI and in the setting of higher SVRI. The E/e′ does not reflect the hemodynamic changes during exercise in HFNEF patients.
It is estimated that approximately 50% of the heart failure population has a normal left ventricular ejection fraction, a complex broadly referred to as heart failure with normal left ventricular ...ejection fraction (HFNEF). While these patients have been considered in epidemiologic studies and clinical trials to represent a single pool of patients, limited more detailed studies indicate that HFNEF patients are a very heterogeneous group, with a number of key pathophysiologic mechanisms. This review summarizes and critically analyzes available data on the pathophysiology of HFNEF, placing it into context with a recently developed diagnostic algorithm. We evaluate the utility of commonly applied echocardiographic measures and biomarkers and integrate mechanistic observations into potential future therapeutic directions.
PDF