Brian A. Houston

Right Ventricular Functional Reserve in Pulmonary Arterial Hypertension

Background— Right ventricular (RV) functional reserve affects functional capacity and prognosis in patients with pulmonary arterial hypertension (PAH). PAH associated with systemic sclerosis (SSc-PAH) has a substantially worse prognosis than idiopathic PAH (IPAH), even though many measures of resting RV function and pulmonary vascular load are similar. We therefore tested the hypothesis that RV functional reserve is depressed in SSc-PAH patients. Methods and Results— RV pressure-volume relations were prospectively measured in IPAH (n=9) and SSc-PAH (n=15) patients at rest and during incremental atrial pacing or supine bicycle ergometry. Systolic and lusitropic function increased at faster heart rates in IPAH patients, but were markedly blunted in SSc-PAH. The recirculation fraction, which indexes intracellular calcium recycling, was also depressed in SSc-PAH (0.32±0.05 versus 0.50±0.05; P=0.039). At matched exercise (25 W), SSc-PAH patients did not augment contractility (end-systolic elastance) whereas IPAH did (P<0.001). RV afterload assessed by effective arterial elastance rose similarly in both groups; thus, ventricular-vascular coupling declined in SSc-PAH. Both end-systolic and end-diastolic RV volumes increased in SSc-PAH patients to offset contractile deficits, whereas chamber dilation was absent in IPAH (+37±10% versus +1±8%, P=0.004, and +19±4% versus –1±6%, P<0.001, respectively). Exercise-associated RV dilation also strongly correlated with resting ventricular-vascular coupling in a larger cohort. Conclusions— RV contractile reserve is depressed in SSc-PAH versus IPAH subjects, associated with reduced calcium recycling. During exercise, this results in ventricular-pulmonary vascular uncoupling and acute RV dilation. RV dilation during exercise can predict adverse ventricular-vascular coupling in PAH patients.

Right ventricular afterload sensitivity dramatically increases after left ventricular assist device implantation: A multi-center hemodynamic analysis

BACKGROUND Right ventricular (RV) failure is a source of morbidity and mortality after left ventricular assist device (LVAD) implantation. In this study we sought to define hemodynamic changes in afterload and RV adaptation to afterload both early after implantation and with prolonged LVAD support. METHODS We reviewed right heart catheterization (RHC) data from participants who underwent continuous-flow LVAD implantation at our institutions (n = 244), excluding those on inotropic or vasopressor agents, pulmonary vasodilators or additional mechanical support at any RHC assessment. Hemodynamic data were assessed at 5 time intervals: (1) pre-LVAD (within 6 months); (2) early post-LVAD (0 to 6 months); (3) 7 to 12 months; (4) 13 to 18 months; and (5) very late post-LVAD (18 to 36 months). RESULTS Sixty participants met the inclusion criteria. All measures of right ventricular load (effective arterial elastance, pulmonary vascular compliance and pulmonary vascular resistance) improved between the pre- and early post-LVAD time periods. Despite decreasing load and pulmonary artery wedge pressure (PAWP), RAP remained unchanged and the RAP:PAWP ratio worsened early post-LVAD (0.44 [0.38, 0.63] vs 0.77 [0.59, 1.0], p < 0.001), suggesting a worsening of RV adaptation to load. With continued LVAD support, both RV load and RAP:PAWP decreased in a steep, linear and dependent manner. CONCLUSIONS Despite reducing RV load, LVAD implantation leads to worsened RV adaptation. With continued LVAD support, both RV afterload and RV adaptation improve, and their relationship remains constant over time post-LVAD. These findings suggest the RV afterload sensitivity increases after LVAD implantation, which has major clinical implications for patients struggling with RV failure.

Clinician's Guide to the Updated ABCs of Cardiovascular Disease Prevention

To facilitate the guideline-based implementation of treatment recommendations in the ambulatory setting and to encourage participation in the multiple preventive health efforts that exist, we have organized several recent guideline updates into a simple ABCDEF approach. We would remind clinicians that evidence-based medicine is meant to inform recommendations but that synthesis of patient-specific data and use of appropriate clinical judgment in each individual situation is ultimately preferred.

Cardiac Sarcoidosis: Clinical Manifestations, Imaging Characteristics, and Therapeutic Approach

Sarcoidosis is a multi-system disease pathologically characterized by the accumulation of T-lymphocytes and mononuclear phagocytes into the sine qua non pathologic structure of the noncaseating granuloma. Cardiac involvement remains a key source of morbidity and mortality in sarcoidosis. Definitive diagnosis of cardiac sarcoidosis, particularly early enough in the disease course to provide maximal therapeutic impact, has proven a particularly difficult challenge. However, major advancements in imaging techniques have been made in the last decade. Advancements in imaging modalities including echocardiography, nuclear spectroscopy, positron emission tomography, and magnetic resonance imaging all have improved our ability to diagnose cardiac sarcoidosis, and in many cases to provide a more accurate prognosis and thus targeted therapy. Likewise, therapy for cardiac sarcoidosis is beginning to advance past a “steroids-only” approach, as novel immunosuppressant agents provide effective steroid-sparing options. The following focused review will provide a brief discussion of the epidemiology and clinical presentation of cardiac sarcoidosis followed by a discussion of up-to-date imaging modalities employed in its assessment and therapeutic approaches.

Hypertrophic Cardiomyopathy: A Review

Hypertrophic cardiomyopathy (HCM) is a global disease with cases reported in all continents, affecting people of both genders and of various racial and ethnic origins. Widely accepted as a monogenic disease caused by a mutation in 1 of 13 or more sarcomeric genes, HCM can present catastrophically with sudden cardiac death (SCD) or ventricular arrhythmias or insidiously with symptoms of heart failure. Given the velocity of progress in both the fields of heart failure and HCM, we present a review of the approach to patients with HCM, with particular attention to those with HCM and the clinical syndrome of heart failure.

Metabolomics of urinary tract infection: a new uroscope in town

Urinary tract infection (UTI) is a potentially life-threatening infectious disease. For rapid directed therapy of UTIs, it is essential to determine the causative microorganism. To date, there is no single test that has been proven to reliably, rapidly and accurately identify the etiologic organism in UTI. The molecular methods for diagnosing the cause of UTI and prognostic development of clinically important metabolomic evaluations and their limitations for use in the diagnosis and monitoring of infections are discussed in this review article. The application of the emerging investigative device NMR spectroscopy as a surrogate method for the diagnosis of UTI is also addressed.

Volume Overload in Heart Failure: An Evidence-Based Review of Strategies for Treatment and Prevention

Acute decompensated heart failure is the leading cause of hospital admission in the United States, with a high risk of readmission within 30 days. Most acute decompensated heart failure admissions are driven by congestive signs and symptoms resulting from fluid and sodium overload. We reviewed the evidence base addressing the management and prevention of fluid overload in heart failure, focusing on recent clinical trials. All the references in this review were obtained through PubMed and had at least 1 of the following key words: heart failure and volume overload, congestion, loop diuretics, thiazide diuretics, aldosterone antagonists, dopamine, cardiorenal syndrome, nesiritide, vasopressin antagonists, ultrafiltration, sodium restriction, fluid restriction, telemonitoring, and invasive hemodynamic monitoring. We also reviewed relevant references cited in the obtained articles, especially articles addressing methods of treating or preventing volume overload in patients with heart failure.

Angiotensin II antagonism is associated with reduced risk for gastrointestinal bleeding caused by arteriovenous malformations in patients with left ventricular assist devices

BACKGROUND Angiogenesis is implicated in formation of gastrointestinal arteriovenous malformations (AVMs). Angiotensin II signaling is involved in angiogenesis through the vascular endothelial growth factor (VEGF) and angiopoietin-2 pathways. We hypothesized that angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy would be associated with a reduced risk of all-cause gastrointestinal bleeding (GIB) and AVM-associated GIB in patients with left ventricular assist devices (LVADs). METHODS We reviewed records of all adult patients receiving a continuous-flow LVAD (HeartMate II or HeartWare HVAD) at Johns Hopkins Hospital between January 2004 and December 2014. Of 192 patients, 131 were included for final analyses. Logistic regression analysis adjusting for demographic, cardiovascular, and laboratory variables was used to assess the association of ACEI or ARB therapy with GIB. RESULTS Of 131 patients, 100 received ACEI or ARB therapy during LVAD support. Of the 31 patients who did not receive ACEI or ARB, 15 experienced GIB (48%), with 9 caused by AVMs (29%). Of 100 patients who received ACEI or ARB therapy, 24 experienced GIB (24%), with 9 caused by AVMs (9%). Logistic regression hazards model demonstrated that ACEI or ARB therapy was independently associated with a reduced risk for all-cause GIB (odds ratio 0.29, 95% confidence interval 0.12-0.72) and AVM-related GIB (odds ratio 0.23, 95% confidence interval 0.07-0.71). CONCLUSIONS Angiotensin II antagonism is associated with a reduced risk of AVM-related GIB in patients with LVADs. This association is independent of age, sex, blood pressure, renal function, international normalized ratio, LVAD type, and cardiomyopathy etiology.

What We Talk About When We Talk About the Wedge Pressure

See Articles by Wright et al and Naeije et al There is a joke that goes something like this: A mathematician, a statistician, and an economist all apply for the same job. The interviewer asks them all the same question: “What is two plus two?” The mathematician, without much thought, answers, “Four.” When the interviewer says, “Four exactly?” the mathematician, with a touch of incredulity replies, “Of course.” The statistician says, “Four, plus or minus ten percent. But on average, four.” When asked “What is two plus two?” the economist stands up, locks the door, closes the shades, and says “What do you want it to be?” As highlighted in a careful study by Wright et al,1 in this issue of Circulation: Heart Failure , we need to decide what we want the pulmonary arterial wedge pressure (PAWP) to be, or more precisely, how we want it to be measured and what we want it to tell us. The current study takes a novel approach to investigate the controversial parameter of diastolic pressure difference, in particular focusing on how variations in measurement techniques affect hemodynamic assessment and disease classification.1 The diastolic pressure difference, more commonly referred to as the diastolic pulmonary gradient (DPG), has risen to prominence as a marker of pulmonary vascular disease in the setting of left heart failure through sound physiological reasoning. As first suggested by Naeije et al2 in 2013, the more traditional markers of pulmonary vascular disease “out-of-proportion” to left heart disease (transpulmonary gradient [TPG] and pulmonary vascular resistance) are fraught with physiological concerns. The TPG, defined as mean pulmonary artery pressure minus the PAWP, does not account for flow state or the …

Pump speed modulations and sub-maximal exercise tolerance in left ventricular assist device recipients: A double-blind, randomized trial

BACKGROUND The effect of pump speed increase on sub-maximal exercise tolerance, corresponding to activities of daily living (ADLs), is unknown. The aim of this study was to determine the effects of increasing pump speed during exercise at a sub-maximal level below anaerobic threshold (AT). METHODS Patients each completed 3 exercise sessions on an ergometer cycle. On Day 1 workload at AT was defined. On Day 2 of the study, 2 sub-maximal tests at a workload below AT were undertaken: one at fixed baseline pump speed (Speedbase) and the other with baseline pump speed + 800 rpm (Speedinc). The sequence of the 2 sub-maximal tests was determined by randomization. Both patient and physician were blinded to the sequence. Exercise duration, oxygen consumption (VO2) and rate of perceived exertion (RPE), using the Borg scale (score 6 to 20), were recorded. RESULTS Nineteen patients (all with a HeartMate II ventricular assist device) completed 57 exercise tests. Baseline pump speed was 9,326 ± 378 rpm. At AT, workload was 63 ± 26 W (25 to 115 W) and VO2 was 79 ± 14% of maximum. Exercise duration improved by 106 ± 217 seconds (~13%) in Speedinc compared with Speedbase (837 ± 358 vs 942 ± 359 seconds; p = 0.048). The RPE was 13.2 ± 2.5 in Speedbase vs 12.7 ± 2.4 in Speedinc (p = 0.2). CONCLUSION Increasing pump speed by 800 rpm during sustained, low-intensity physical activity is safe and prolongs exercise duration in patients supported with a HeartMate II device. Automated pump speed increase during light exercise may contribute to improved quality of life by facilitating ADLs.