V.N. Selby

The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease.

OBJECTIVES This study sought to evaluate if diastolic pulmonary gradient (DPG) can predict survival in patients with pulmonary hypertension due to left heart disease (PH-LHD). BACKGROUND Patients with combined post- and pre-capillary PH-LHD have worse prognosis than those with passive pulmonary hypertension. The transpulmonary gradient (TPG) and pulmonary vascular resistance (PVR) have commonly been used to identify high-risk patients. However, these parameters have significant shortcomings and do not always correlate with pulmonary vasculature remodeling. Recently, it has been suggested that DPG may be better a marker, yet its prognostic ability in patients with cardiomyopathy has not been fully assessed. METHODS A retrospective cohort of 1,236 patients evaluated for unexplained cardiomyopathy at Johns Hopkins Hospital was studied. All patients underwent right heart catheterization and were followed until death, cardiac transplantation, or the end of the study period (mean time 4.4 years). The relationships between DPG, TPG, or PVR and survival in subjects with PH-LHD (n = 469) were evaluated with Cox proportional hazards regression and Kaplan-Meier analyses. RESULTS DPG was not significantly associated with mortality (hazard ratio [HR]: 1.02, p = 0.10) in PH-LHD whereas elevated TPG and PVR predicted death (HR: 1.02, p = 0.046; and HR: 1.11, p = 0.002, respectively). Similarly, DPG did not differentiate survivors from non-survivors at any selected cut points including a DPG of 7 mm Hg. CONCLUSIONS In this retrospective study of patients with cardiomyopathy and PH-LHD, an elevated DPG was not associated with worse survival.

The association of CD4+ T-cell counts and cardiovascular risk in treated HIV disease.

Objective:HIV-infected individuals are at high risk of developing cardiovascular disease. Whether earlier initiation of HIV therapy at higher CD4+ cell counts has any effect on cardiovascular risk as assessed by endothelial function is unknown. Design:Cross-sectional study of 74 antiretroviral-treated men with undetectable plasma HIV RNA levels. Methods:Participants underwent noninvasive assessment of endothelial function using brachial artery flow-mediated dilation (FMD). The association of nadir and current CD4+ T-cell count with FMD was assessed using multivariable linear regression. Results:The median age was 47 years [interquartile range (IQR) 42–55], median current CD4+ T-cell count was 659 cells/&mgr;l (IQR 542–845), and nadir CD4 cell count was 314 cells/&mgr;l (IQR 150–490). Twenty-eight percent had hypertension, and 32% hyperlipidemia. Nadir CD4+ T-cell count less than 350 cells/&mgr;l was associated with lower FMD in age-adjusted and race-adjusted analyses and remained an independent predictor of FMD after adjustment for cardiovascular risk factors (hypertension, diabetes, smoking, hyperlipidemia) and HIV-related characteristics (HIV duration, HAART duration). After multivariable adjustment, individuals with nadir CD4+ T-cell count less than 350 cells/&mgr;l had a 1.22% lower FMD compared with those with higher T-cell counts [95% confidence interval (CI) −2.20 to −0.19, P = 0.02]. Proximal CD4+ T-cell count showed little association with FMD. Conclusion:Among treated HIV-infected individuals, nadir CD4+ T-cell count less than 350 cells/&mgr;l is independently associated with lower FMD, suggesting that delayed therapy results in sustained harm to endothelial function. Our data support future prospective studies evaluating cardiovascular effects of HAART initiation at higher CD4+ cell counts.

Carotid Intima-Media Thickness Among Human Immunodeficiency Virus–Infected Patients Without Coronary Calcium

Subjects infected with human immunodeficiency virus (HIV) have increased risk for atherosclerosis. Carotid artery intima-media thickness (IMT) assessed using ultrasound and coronary artery calcium (CAC) detected using computed tomography predict cardiovascular risk in the general population; however, their usefulness and comparability in patients with HIV are less well defined. The purpose of this study was to compare IMT and CAC in the detection of atherosclerosis in subjects with HIV. CAC and IMT were measured in 253 HIV-infected and 58 uninfected adults. Associations among HIV-related factors, traditional risk factors, and CAC and IMT were evaluated. The distribution of IMT among subjects with and without CAC was compared. Among the patients with HIV, 37% had detectable CAC compared to 28% of controls (p = 0.19); 16% of the patients with HIV had CAC >100 compared to 5% of controls (p = 0.03). With either detectable or undetectable CAC, HIV-infected subjects had higher IMT compared to controls (1.02 ± 0.34 vs 0.78 ± 0.12 mm, p <0.0001), even after adjustment for traditional risk factors. Among those with undetectable CAC, 34% of patients with HIV had markedly increased IMT (≥1 mm) compared to no controls (p <0.0001). HIV-related factors were associated with IMT but not with CAC. In conclusion, patients with HIV and controls had similar rates of detectable CAC, while absolute CAC scores were modestly higher in the HIV group. Conversely, carotid IMT detected advanced subclinical atherosclerosis in patients with HIV even in the absence of CAC. Thus, with HIV, IMT is associated with disease-related factors and may be a more sensitive indicator of subclinical atherosclerosis than CAC.

Doppler Echocardiography Does Not Accurately Estimate Pulmonary Artery Systolic Pressure in HIV-Infected Patients

Doppler echocardiography is used to screen for HIV-related pulmonary arterial hypertension (HRPAH). We studied patients with HIV infection to determine the accuracy of Doppler echocardiography-estimated pulmonary artery systolic pressure (PASP) compared with PASP measured during right heart catheterization. Doppler echocardiography-estimated PASP was inaccurate in 19.7% of cases. Using Doppler echocardiography-estimated PASP, one in three patients with HRPAH was missed. Doppler echocardiography estimates of PASP are not accurate in patients with HIV.

What’s New in the Treatment of Acute Heart Failure?

Acute heart failure is associated with substantial morbidity and mortality. Goals of treatment are decongestion, correction of hemodynamic abnormalities, symptom relief, and reducing long-term morbidity and mortality. Loop diuretics are a first-line agent for treatment of volume overload, with ultrafiltration reserved for those who do not respond to pharmacologic therapy. In patients with normal or elevated blood pressure, vasodilators are used to correct hemodynamics and reverse central volume redistribution, although no currently available agent has been shown to improve outcomes. Intravenous inotropes and inodilators are associated with frequent adverse effects and are reserved for patients with hypotension and evidence of inadequate perfusion. Novel drugs designed to maximize hemodynamic benefits while minimizing adverse effects are under investigation, with several agents showing promise in clinical studies.

Commentary: Selection Bias in Clinical Epidemiology: Causal Thinking to Guide Patient-centered Research.

The number of patients awaiting heart transplantation in the US has increased by approximately 50% over the past decade. During this same period, the heart transplant rate declined slightly, resulting in a severe shortage of donor organ availability, longer wait times, and a heart transplant waitlist mortality of approximately 10 per 100 waitlist-years. one potential strategy for increasing the supply of hearts is to accept older donors, but this is controversial because of concerns that older donors may have less healthy hearts than younger donors. to choose the optimal transplant upper age-eligibility criterion, we must balance the risk of an unhealthy heart from an older donor against the potential harm of longer-waiting times for a heart, including risk of dying while on the waitlist or impaired post-transplant health due to longer wait time with a failing heart. Unfortunately, neither side of this equation is easy to estimate precisely. Goldstein et al. undertook a clever approach to evaluating the likely consequences of longer waiting times for heart transplantation by using blood type as an instrumental variable (IV). the IV analysis should circumvent unmeasured confounding by factors that may influence both wait time and patient outcomes, such as the providing physician’s “pickiness” with respect to heart quality or the current health of the patient. aBo blood type provides a potential IV for transplant wait times because it is easier to identify an eligible heart if the recipient has a relatively easy-to-match blood type, such as aB, rather than the more difficult-to-match o blood type. Indeed, in their sample, median wait time for a type aB patient was 33 days, compared with 178 days for a blood type o patient, and blood types a and B were intermediate. Previous work has established blood type as an IV for the effect of wait time on other transplant outcomes, effectively treating blood type as a natural experiment for wait time. Goldstein et al. are the first to use this IV in the context of heart transplant. Blood type is an appealing IV because there is no reason that blood type should impact transplant outcomes except via wait time, and blood type should not be associated with other determinants of transplant outcomes. But a valid IV is only defined with respect to estimating the effect of a particular treatment on a particular outcome. In this case, the treatment of interest is longer wait time for a transplant, but what is the outcome of interest for transplant patients? typical transplant research defines the outcome as survival after transplant. In other words, the outcome is undefined for people who die while awaiting a transplant. Indeed, transplant centers are often evaluated based on this criterion: 1-year

Current Treatment Strategies in Pulmonary Hypertension Associated with Left Heart Disease

Pulmonary hypertension (PH) is a common complication of left heart disease (LHD) and is associated with impaired functional capacity and decreased survival. Recent guidelines have proposed a new classification system for PH-LHD that is based on the diastolic pulmonary gradient. Despite a sound physiologic basis, subsequent studies have not found a significant correlation between the diastolic pulmonary gradient and meaningful outcomes. Treatment of PH-LHD focuses on optimizing the left heart disease. The use of medications for the treatment of combined post- and pre-capillary PH in left heart disease is controversial. While several small studies have shown hemodynamic or symptomatic improvement, none have been demonstrated to clearly improve long-term outcomes. Large, event-driven trials of PH-LHD are needed to guide the optimal management of this population.