Daniel G. Blanchard

Correlation of left ventricular diastolic filling characteristics with right ventricular overload and pulmonary artery pressure in chronic thromboembolic pulmonary hypertension.

OBJECTIVES This study was designed to determine a quantitative relationship between right ventricular (RV) pressure overload and left ventricular (LV) diastolic filling characteristics in patients with chronic thromboembolic pulmonary hypertension (CTEPH). BACKGROUND Right ventricular pressure overload in patients with CTEPH causes abnormal LV diastolic filling. However, a quantitative relationship between RV pressure overload and LV diastolic function has not been established. METHODS We analyzed pre- and postoperative diastolic mitral inflow velocities and right heart hemodynamic data in 39 consecutive patients with CTEPH over the age of 30 (55 +/- 11 years) with mean pulmonary artery pressure >30 mm Hg who underwent pulmonary thromboendarterectomy (PTE). RESULTS After PTE, mean pulmonary artery pressure (mPAP) decreased from 50 +/- 11 to 28 +/- 9 mm Hg (p < 0.001) while cardiac output (CO) increased from 4.4 +/- 1.1 to 5.7 +/- 0.9 l/m (p < 0.001). Mitral E/A ratio (E/A) increased from 0.74 +/- 0.22 to 1.48 +/- 0.69 (p < 0.001). E/A was < 1.25 in all patients pre-PTE. After PTE, all patients with E/A >1.50 had mPAP <35 mm Hg and CO >5.0 l/min. E/A correlated inversely with mPAP (r = 0.55, p < 0.001) and directly with CO (r = 0.53, p < 0.001). CONCLUSIONS E/A is consistently abnormal in patients with CTEPH and increases post-PTE. Moreover, E/A varies inversely with mPAP and directly with CO. Following PTE, E/A >1.5 correlates with the absence of severe pulmonary hypertension (mPAP >35 mm Hg) and the presence of normal cardiac output (> 5.0 l/m).

Utility of Right Ventricular Tei Index in the Noninvasive Evaluation of Chronic Thromboembolic Pulmonary Hypertension Before and After Pulmonary Thromboendarterectomy

OBJECTIVES We evaluated the utility of tissue Doppler-derived right ventricular (RV) Tei (or myocardial performance) index in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary thromboendarterectomy (PTE) and assessed correlations with mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO). BACKGROUND The assessment of RV function is limited with 2-dimensional echocardiography. The RV Tei index, an indicator of RV myocardial performance, is derived by Doppler measurements and is unaffected by RV geometry. The use of tissue Doppler imaging (at the lateral tricuspid annulus) for RV Tei index calculation is simple and eliminates the need for pulsed-wave Doppler recordings of both RV inflow and outflow. METHODS Ninety-three patients with CTEPH were prospectively studied along with 13 control patients. Right ventricular tissue Doppler imaging and right heart catheterization were performed before and after PTE. Right ventricular Tei index was compared with values of mPAP, PVR, and CO with the use of linear regression. RESULTS Right ventricular Tei index was 0.52 +/- 0.19 in patients with CTEPH and 0.27 +/- 0.09 in control patients (p < 0.0001). After PTE, RV Tei index decreased to 0.33 +/- 0.10 (p < 0.0001). Pulmonary vascular resistance correlated well with RV Tei index before (r = 0.78, p < 0.0001) and after (r = 0.67, p < 0.0001) surgery. Also, the absolute change in Tei index in each patient after PTE correlated well with the concomitant change in PVR (r = 0.75, p < 0.0001). RV Tei index did not correlate as well with mPAP (pre-operatively: r = 0.55, p < 0.0001; post-operatively: r = 0.26, p = 0.03) or CO (pre-operatively: r = 0.57, p < 0.0001; post-operatively: r = 0.43, p < 0.0001). CONCLUSIONS These results demonstrate a correlation between RV Tei index and right heart hemodynamics (particularly PVR) in CTEPH. Because PVR is difficult to estimate noninvasively -- and yet correlates with disease severity -- the RV Tei index may be a valuable noninvasive parameter for monitoring disease severity in CTEPH and outcome after PTE.

Reversibility of Cardiac Abnormalities in Human Immunodeficiency Virus (HIV)-Infected Individuals: A Serial Echocardiographic Study

Seventy adults who tested positive for human immunodeficiency virus (HIV) were prospectively studied with serial echocardiography to better define the prevalence and progression of cardiac disease in such patients. Fifty outpatients (Group A), including 44 with acquired immunodeficiency syndrome (AIDS) and 6 with AIDS-related complex, and 20 additional patients (Group B) with asymptomatic HIV infection had baseline echocardiographic studies at a time when no patient had symptomatic heart disease. Follow-up studies were performed at 9 +/- 3 months in 52 patients (74%) and again at 15 +/- 3 months after baseline studies in 29 patients (41%). During the study, 22 patients (44%) in Group A and 1 patient (5%) in Group B died. Cardiac abnormalities were noted in 26 patients (52%) in Group A and 8 patients (40%) in Group B (p = NS) on initial or follow-up study. An abnormal left ventricular ejection fraction (less than 45%) or fractional shortening (less than 28%) was seen in seven patients in Group A; of these, three had normal left ventricular function on a later echocardiogram. One patient in Group B had persistent left ventricular dysfunction. All patients in Group A with left ventricular dysfunction on two serial studies died within 1 year after the initial echocardiogram. Ejection fraction did not change between baseline and two follow-up studies in either group (A: 52 +/- 9 vs. 56 +/- 9 vs. 55 +/- 5%, p = NS; B: 58 +/- 6 vs. 58 +/- 5 vs. 59 +/- 6%, p = NS). Right-sided cardiac enlargement resolved in 18 patients (44%), including 5 of 10 in Group A and 3 of 8 in Group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure A Randomized Clinical Trial

IMPORTANCE Gene transfer has rarely been tested in randomized clinical trials. OBJECTIVE To evaluate the safety and efficacy of intracoronary delivery of adenovirus 5 encoding adenylyl cyclase 6 (Ad5.hAC6) in heart failure. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled, phase 2 clinical trial was conducted in US medical centers (randomization occurred from July 19, 2010, to October 30, 2014). Participants 18 to 80 years with symptomatic heart failure (ischemic and nonischemic) and an ejection fraction (EF) of 40% or less were screened; 86 individuals were enrolled, and 56 were randomized. Data analysis was of the intention-to-treat population. Participants underwent exercise testing and measurement of left ventricular EF (echocardiography) and then cardiac catheterization, where left ventricular pressure development (+dP/dt) and decline (-dP/dt) were recorded. Participants were randomized (3:1 ratio) to receive 1 of 5 doses of intracoronary Ad5.hAC6 or placebo. Participants underwent a second catheterization 4 weeks later for measurement of dP/dt. Exercise testing and EF were assessed 4 and 12 weeks after randomization. INTERVENTIONS Intracoronary administration of Ad5.hAC6 (3.2 × 109 to 1012 virus particles) or placebo. MAIN OUTCOMES AND MEASURES Primary end points included exercise duration and EF before and 4 and 12 weeks after randomization and peak rates of +dP/dt and -dP/dt before and 4 weeks after randomization. Fourteen placebo participants were compared (intention to treat) with 24 Ad5.hAC6 participants receiving the highest 2 doses (D4 + 5). RESULTS Fifty-six individuals were randomized and monitored for up to 1 year. Forty-two participants (75%) received Ad5.hAC6 (mean [SE] age, 63 [1] years; EF, 30% [1%]), and 14 individuals (25%) received placebo (age, 62 [1] years; EF, 30% [2%]). Exercise duration showed no significant group differences (4 weeks, P = .27; 12 weeks, P = .47, respectively). The D4 + 5 participants had increased EF at 4 weeks (+6.0 [1.7] EF units; n = 21; P < .004), but not 12 weeks (+3.0 [2.4] EF units; n = 21; P = .16). Placebo participants showed no increase in EF at 4 weeks or 12 weeks. Exercise duration showed no between-group differences (4-week change from baseline: placebo, 27 [36] seconds; D4 + 5, 44 [25] seconds; P = .27; 12-week change from baseline: placebo, 44 [28] seconds; D4 + 5, 58 [29 seconds, P = .47). AC6 gene transfer increased basal left ventricular peak -dP/dt (4-week change from baseline: placebo, +93 [51] mm Hg/s; D4 + 5, -39 [33] mm Hg/s; placebo [n = 21]; P < .03); AC6 did not increase arrhythmias. The admission rate for patients with heart failure was 9.5% (4 of 42) in the AC6 group and 28.6% (4 of 14) in the placebo group (relative risk, 0.33 [95% CI, 0.08-1.36]; P = .10). CONCLUSIONS AND RELEVANCE AC6 gene transfer safely increased LV function beyond standard heart failure therapy, attainable with one-time administration. Larger trials are warranted. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00787059.

Left ventricular underfilling and not septal bulging dominates abnormal left ventricular filling hemodynamics in chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is associated with abnormal left ventricular (LV) filling hemodynamics [mitral early passive filling wave velocity/late active filling wave velocity (E/A) < 1]. Pulmonary endarterectomy (PEA) acutely reduces pulmonary vascular resistance, resulting in an increase of mitral E/A. The abolishment of leftward septal bulging and an increase in right ventricular (RV) output are thought to be responsible for the increase of mitral E/A. In this study, we quantified the separate effects of leftward septal bulging and RV output on LV hemodynamics. In 39 CTEPH patients who underwent PEA, transmitral flow velocities and RV hemodynamic data were obtained pre- and postoperatively. A mathematical model describing the mechanics of ventricular interaction was fitted to the preoperative average values of cardiac output (CO; 4.4 l/min), mean pulmonary artery pressure (mPAP; 50 mmHg), mitral E/A (0.74), and mean left atrial pressure (mLAP; 9.8 mmHg). Starting from this preoperative reference state with leftward septal bulging, PEA was simulated by changing mPAP and CO to average postoperative values (28 mmHg and 5.7 l/min, respectively). Simulated and postoperatively measured data on E/A (1.27 vs. 1.48), mLAP (12.6 vs. 11.5 mmHg), and septal curvature (both rightward) were consistent. When an exclusive decrease of mPAP was simulated, mitral E/A increased 26%, mLAP decreased 16%, and septal curvature became rightward. When an exclusive increase of CO was simulated, mitral E/A increased 53% and mLAP increased 62%, whereas leftward septal bulging persisted. Thus, our simulations suggest that the increase of mitral E/A with PEA is caused two-thirds by an increase of RV output and one-third by the abolishment of leftward septal bulging.

Recurrent Kawasaki Disease—like Syndrome in a Patient with Acquired Immunodeficiency Syndrome

A review of Kawasaki disease (KD)-like syndromes (KDLS) in patients with human immunodeficiency virus (HIV) raised the question whether vasculitis in children and KDLS in immunocompromised adults might be etiologically related. We describe a 42-year-old white man with AIDS and Kaposi sarcoma who presented with KDLS, which was diagnosed on the basis of clinical criteria for KD. Analysis of a conjunctival tissue sample revealed endothelial cell damage with fibrin deposition and infiltration of immunoglobulin A-secreting plasma cells.

Cardiac Limited Ultrasound Examination Techniques to Augment the Bedside Cardiac Physical Examination

The current practice of physical diagnosis is dependent on physician skills and biases, inductive reasoning, and time efficiency. Although the clinical utility of echocardiography is well known, few data exist on how to integrate 2‐dimensional screening “quick‐look” ultrasound applications into a novel, modernized cardiac physical examination. We discuss the evidence basis behind ultrasound “signs” pertinent to the cardiovascular system and elemental in synthesis of bedside diagnoses and propose the application of a brief cardiac limited ultrasound examination based on these signs. An ultrasound‐augmented cardiac physical examination can be taught in traditional medical education and has the potential to improve bedside diagnosis and patient care.

Infrahepatic Interruption of the Inferior Vena Cava with Azygos Continuation: A Potential Mimicker of Aortic Pathology

Infrahepatic interruption of the inferior vena cava (IVC) with azygos or hemiazygos continuation is a rare finding. In this anatomic entity, the intrahepatic segment of the IVC is absent, and the hepatic veins empty directly into the right atrium. Venous blood flow from the lower body is directed from the IVC into the azygos system at the level of the renal veins, with resultant dilation of the azygos and/or hemiazygos veins. Because these enlarged vessels lie parallel to the descending thoracic aorta, they may be mistaken for aortic pathology (dissection, aneurysm, or rupture) during transesophageal echocardiography (TEE). We describe a case of azygos continuation of the IVC initially misdiagnosed by TEE as partial aortic rupture. Repeat TEE with intravenous agitated saline injection correctly identified the condition, and the echocardiographic features are described.

Left ventricular strain and strain rate by 2D speckle tracking in chronic thromboembolic pulmonary hypertension before and after pulmonary thromboendarterectomy

BackgroundEchocardiographic evaluation of left ventricular (LV) strain and strain rate (SR) by 2D speckle tracking may be useful tools to assess chronic thromboembolic pulmonary hypertension (CTEPH) severity as well as response to successful pulmonary thromboendarterectomy (PTE).MethodsWe evaluated 30 patients with CTEPH before and after PTE using 2D speckle tracking measurements of LV radial and circumferential strain and SR in the short axis, and correlated the data with right heart catheterization (RHC).ResultsPTE resulted in a decrease in mean PA pressure (44 ± 15 to 29 ± 9 mmHg), decrease in PVR (950 ± 550 to 31 ± 160 [dyne-sec]/cm5), and an increase in cardiac output (3.9 ± 1.0 to 5.0 ± 1.0 L/min, p < 0.001 for all). Circumferential and posterior wall radial strain changed by -11% and +15% respectively (p < 0.001 for both). Circumferential SR and posterior wall radial SR changed by -7% and 6% after PTE. While the increase in posterior wall SR with PTE reached statistical significance (p = 0.04) circumferential SR did not (p = 0.07). In addition, septal radial strain and SR did not change significantly after PTE (p = 0.1 and 0.8 respectively). Linear regression analyses of circumferential and posterior wall radial strain and SR revealed little correlation between strain/SR measurements and PVR, mean PA pressure, or cardiac output. However, change in circumferential strain and change in posterior wall radial strain correlated moderately well with changes in PVR, mean PA pressure and cardiac output (r = 0.69, 0.76, and 0.51 for circumferential strain [p < 0.001 for all] and r = 0.7, 0.7, 0.45 for posterior wall radial strain [p = 0.001, 0.001, and 0.02, respectively]).ConclusionsLV circumferential and posterior wall radial strain change after relief of pulmonary arterial obstruction in patients with CTEPH, and these improvements occur rapidly. These changes in LV strain may reflect effects from improved LV diastolic filling, and may be useful non-invasive markers of successful PTE.

The hemodynamic basis of diastology

by C. P. Appleton, L. K. Hatle, R. I. Popp [(2)][1] Introduction In this edition of the Journal , we release the thirteenth in a series of reviews of influential articles that have been previously published in ACC journals, including the American Journal of Cardiology (from 1958 to 1982) and JACC