Statin therapy improves survival in patients with severe pulmonary hypertension: a propensity score matching study.

Inflammation is an increasingly recognized hallmark of pulmonary hypertension (PH). Statins have been shown to attenuate key pathologic mechanisms via pleiotropic effects in animal models. However, clinical benefit of statins in patients with PH is unknown and their effect on mortality has not been studied. We performed a retrospective analysis of patients between January 2002 to January 2012, with severe PH (pulmonary artery systolic pressure ≥60 mmHg) and preserved left ventricular function (ejection fraction ≥50%), defined by transthoracic echocardiograms. Patients were divided into two groups based on statin therapy for 12 consecutive months after diagnosis of PH. Propensity score matching was performed. Subgroup analysis was done based on COPD status. Study endpoint was 1-year all-cause mortality and hospitalization. 2363 patients (age 71 ± 16; 31% male) were included; 140 (6%) were on statin therapy. Overall 1-year mortality was 34%. Following propensity score matching, 138 patients were included in the statin group and 624 patients in the no-statin group; all-cause mortality was significantly lower in the statin group compared with the no-statin group [15.2 vs. 33.8%, HR 0.42 (95% CI 0.27, 0.66), p < 0.001], but hospitalization was comparable between two groups. After stratifying patients based on COPD status, patients with COPD showed a marginally significant survival benefit from statins [HR 0.53 (95% CI 0.26, 1.10), p = 0.09]; and statins significantly reduced 1-year all-cause mortality in patients without COPD [HR 0.36 (95% CI 0.19, 0.67), p = 0.001]. We found no significant difference in the effect of statins on patients with COPD compared to those without (p = 0.16). Statin therapy is associated with reduced mortality risk in patients with severe PH and preserved left ventricular function. This beneficial effect was not found to be dependent on COPD status. These novel findings should be confirmed in large randomized trials.

Addition of angiotensin-converting enzyme inhibitors to beta-blockers has a distinct effect on hispanics compared with african americans and whites with heart failure and reduced ejection fraction: a propensity score-matching study.

BACKGROUND: There are currently no data on the efficacy of angiotensin-converting enzyme inhibitors (ACEis) in Hispanic patients with heart failure (HF) and reduced ejection fraction (HFrEF). We aimed to investigate the effect of adding ACEis to beta-blockers on mortality and hospitalization for HF exacerbation in patients with HFrEF stratified by race/ethnicity. METHODS AND RESULTS: From Montefiore Medical Center's 3 large hospitals, 618 consecutive patients with HFrEF (left ventricular ejection fraction [LVEF] <35%) who were on a beta-blocker were retrospectively identified. Patients were divided into 2 groups based on whether or not they were on an ACEi for 24 consecutive months. Propensity score matching including all baseline characteristics was performed and patients were then categorized into 3 groups: African Americans, Hispanics, and Whites/Caucasians. We evaluated 2-year all-cause mortality and 2-year hospitalization for HF exacerbation. Of 618 patients, 66% were categorized as ACEi and 34% as no-ACEi. Four hundred twenty-seven patients were matched 2:1 between the ACEi and no-ACEi groups. After matching, overall 2-year mortality and hospitalization rates were similar between ACEi and no-ACEi (12.4% vs 17.8%, hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.38-1.16; P = .14; and 8.1% vs 9.5%, HR 0.84, 95% CI 0.44-1.60; P = .6; respectively). After stratifying patients based on race/ethnicity, ACEi demonstrated a lower 2-year mortality compared with no-ACEi in Hispanics (9.8% vs 28.4%, HR 0.33, 95% CI 0.13-0.87; P = .018) but not in African Americans (17.0% vs 11.8%, HR 0.94, 95% CI 0.34-2.65; P = .91) or Whites (9.2% vs 10.3%, HR 0.89, 95% CI 0.29-2.74; P = .83). Two-year hospitalization was not different between ACEi and no-ACEi in Hispanics, African Americans, or Whites (all P = NS). In multivariate analysis, ACEi therapy was an independent predictor of lower 2-year mortality (HR 0.33, 95% CI 0.12-0.89; P = .028) in Hispanics only. CONCLUSIONS: In this retrospective propensity-matched study of patients with HFrEF who were on a beta-blocker, ACEi therapy was associated with greater mortality reduction in Hispanic patients compared with African Americans and Whites. These findings need to be confirmed in large national studies that include a significant fraction of Hispanic patients.

Sensitivity of brachial versus femoral vein injection of agitated saline to detect right-to-left shunts with Transcranial Doppler.

BACKGROUND: Transcranial Doppler (TCD) can detect a right-to-left shunt (RLS) with high sensitivity but has a 5% chance of a false negative study. TCD is usually performed with injection of agitated saline into an arm vein. We compared the sensitivity of TCD performed from the brachial versus femoral veins. METHODS: Patients presenting to the cardiac catheterization laboratory for percutaneous closure of a patent foramen ovale (PFO) were enrolled. Power M-mode Transcranial Doppler (Terumo 150 PMD) was conducted. After injection of a mixture of 8 cc of agitated saline, 0.5 cc of air, and 1 cc of blood into the brachial vein, embolic tracks were counted over the middle cerebral arteries. The degree of RLS was evaluated by TCD at rest, and with Valsalva at 40 mmHg aided by visual feedback with a manometer device. The test was repeated using femoral venous injections. RESULTS: Sixty five patients were enrolled, mean age 52, 43% male. TCD grades were significantly higher with femoral injections compared to brachial injections at rest (p<0.0001), and with the Valsalva maneuver (p<0.0001). The presence of a RLS was confirmed by intracardiac echocardiography (ICE) during cardiac catheterization in 62 (95.4%) patients. CONCLUSION: The sensitivity of TCD for detection of RLS is increased when agitated saline injections are performed through the femoral vein. In patients with a high clinical suspicion for RLS, low TCD grades obtained with traditional brachial venous access should be interpreted with caution. When possible, a repeat study using femoral venous access may be considered.

Incidence of patent foramen ovale and migraine headache in adults with congenital heart disease with no known cardiac shunts.

The purpose of this study was to understand why patients with adult congenital heart disease (CHD) but no obvious shunt have an increased frequency of migraine headaches (MH). CHD patients with no known cardiac shunts (CHD-NKS), based on their echocardiographic or angiographic procedures, were tested for a right-to-left shunt using agitated saline contrast transcranial Doppler (TCD). Medical records of 2,920 patients from the UCLA Adult CHD Center were screened to participate in a study to evaluate the prevalence of MH in adults with CHD; 182 patients (6.23%) had CHD-NKS; of these, 60 (30%) underwent a TCD; 23 (38%) tested positive and 37 (62%) tested negative for a right-to-left shunt (P = 0.01 compared with controls). The frequency of MH was 43% in CHD-NKS compared with 11% in controls (P < 0.0001). TCD demonstrated right-to-left shunting in approximately 2/3 of patients with pulmonary stenosis, the Marfan syndrome and congenitally corrected transposition of great vessels, 1/4 of patients with bicuspid aortic valve, 1/5 of patients with mitral valve prolapse and all patients with Ebstein's anomaly. Approximately half of these experienced MH. Patients who had MH did not show a higher frequency of right-to-left shunt when compared with patients without MH (P = 0.57). In conclusion, CHD patients with conditions usually not associated with a shunt have a higher than expected prevalence of PFO which permits intermittent right-to-left shunting undetected by standard non-contrast TTE and TEE; the increased prevalence of right-to-left shunting may partially explain the higher than expected frequency of migraines.

Non-invasive assessment of low risk acute chest pain in the emergency department: A comparative meta-analysis of prospective studies.

BACKGROUND: The aim of this meta-analysis was to compare the diagnostic accuracy of cardiac computed tomographic angiography (CCTA), stress echocardiography (SE) and radionuclide single photon emission computed tomography (SPECT) for the assessment of chest pain in emergency department (ED) setting. METHODS: A systematic review of Medline, Cochrane and Embase was undertaken for prospective clinical studies assessing the diagnostic efficacy of CCTA, SE or SPECT, as compared to intracoronary angiography (ICA) or the later presence of major adverse clinical outcomes (MACE), in patients presenting to the ED with chest pain. Standard approach and bivariate analysis were performed. RESULTS: Thirty-seven studies (15 CCTA, 9 SE, 13 SPECT) comprising a total of 7800 patients fulfilled inclusion criteria. The respective weighted mean sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and total diagnostic accuracy for CCTA were: 95%, 99%, 84%, 100% and 99%, for SE were: 84%, 94%, 73%, 96% and 96%, and for SPECT were: 85%, 86%, 57%, 95% and 88%. There was no significant difference between modalities in terms of NPV. Bivariate analysis revealed that CCTA had statistically greater sensitivity, specificity, PPV and overall diagnostic accuracy when compared to SE and SPECT. CONCLUSIONS: All three modalities, when employed by an experienced clinician, are highly accurate. Each has its own strengths and limitations making each well suited for different patient groups. CCTA has higher accuracy than SE and SPECT, but it has many drawbacks, most importantly its lack of physiologic data.

Accuracy of transcranial Doppler for the diagnosis of intracardiac right-to-left shunt: a bivariate meta-analysis of prospective studies.

OBJECTIVES: The aim of this meta-analysis was to determine the accuracy of transcranial Doppler (TCD) compared with transesophageal echocardiography (TEE) as the reference. BACKGROUND: Right-to-left shunting (RLS), usually through a patent foramen ovale (PFO), has been associated with migraine, cryptogenic stroke, and hypoxemia. With emerging observational studies and clinical trials on the subject of PFO, there is a need for accurate diagnosis of PFO in patients with these conditions, and those being considered for transcatheter closure. Although a TEE bubble study is the current standard reference for diagnosing PFO, the TCD bubble study may be a preferable alternative test for RLS because of its high sensitivity and specificity, noninvasive nature, and low cost. METHODS: A systematic review of Medline, the Cochrane Library, and Embase was done to look for all the prospective studies assessing intracardiac RLS using TCD compared with TEE as the reference; both tests were performed with a contrast agent and a maneuver to provoke RLS in all studies. RESULTS: A total of 27 studies (29 comparisons) with 1,968 patients (mean age 47.8 ± 5.7 years; 51% male) fulfilled the inclusion criteria. The weighted mean sensitivity and specificity for TCD were 97% and 93%, respectively. Likewise, the positive and negative likelihood ratios were 13.51 and 0.04, respectively. When 10 microbubbles was used as the embolic cutoff for a positive TCD study, TCD produced a higher specificity compared with when 1 microbubble was used as the cutoff (p = 0.04); there was, however, no significant change in sensitivity (p = 0.29). CONCLUSIONS: TCD is a reliable, noninvasive test with excellent diagnostic accuracies, making it a proficient test for detecting RLS. TCD can be used as a part of the stroke workup and for patients being considered for PFO closure. If knowledge of the precise anatomy is required, then TEE can be obtained before scheduling a patient for transcatheter PFO closure.

Visual migraine aura with or without headache: association with right to left shunt and assessment following transcutaneous closure.

BACKGROUND: Right to left shunting, usually caused by a patent foramen ovale (PFO), is associated with migraine and visual aura. It is unknown if patients who present with visual aura without headache behave similarly to those experiencing typical migraine headache with aura. The purpose of this study was to assess the prevalence of right to left shunting in patients who present with migraine aura without headache and evaluate the response to PFO closure. METHODS: The records of patients referred to the Interventional Cardiology program at the University of California at Los Angeles for suspected intracardiac right to left shunt were reviewed. Individuals with visual auras with or without migraine headaches were divided into three groups: group A (aura + migraine), migraine aura during or within 60 minutes of headache; group B (migraine aura unrelated to headache), migraine aura and headache temporally unrelated; and group C (migraine aura only), isolated migraine visual aura without a history of headaches. The presence of right to left shunt was assessed using transcranial Doppler with an agitated saline test. PFO closure was performed in 80 patients. Residual headache and migraine visual aura were assessed 3 and 12 months after the procedure. The control group consisted of 200 patients referred for diagnostic cardiac catheterization. RESULTS: Of 590 referred patients, 225 had migraine visual aura with or without headache. The prevalence of right to left shunt was similar (P = 0.66) in groups B (21/29, 72%) and C (14/21, 67%). Group A patients had a higher prevalence of right to left shunt (168/175, 96%) due to selection bias. The prevalence of right to left shunt in the control group was significantly (P < 0.0001) lower (36/200, 18%) than in groups A, B, and C. At 12 months after PFO closure, visual aura was resolved in 52%, 75%, and 80% of patients in groups A, B, and C, respectively (difference not statistically significant). CONCLUSION: There is an increased prevalence of PFO among patients with migraine aura without headache. The closure of PFO correlates with improvement of the visual aura, suggesting a causative association between the presence of PFO and both visual aura and migraine headaches. Ophthalmologists should be aware of the association of right to left shunts with visual aura.

The effect of patent foramen ovale closure on visual aura without headache or typical aura with migraine headache.

OBJECTIVES: The aim of this study was to assess the prevalence of right-to-left (R to L) shunt in patients with visual aura and evaluate the effect of shunt closure on resolution of aura. BACKGROUND: Right-to-left shunting is associated with migraine headache (MH) with aura. Some patients present with visual aura without headaches. It is unclear whether visual aura without headache is a form of migraine or a transient neurologic dysfunction. METHODS: Of patients referred to the University of California, Los Angeles for suspected patent foramen ovale (PFO), 225 had visual aura with or without MH. Patients were assessed for a shunt and evaluated for MH and/or visual aura. They were divided into 3 groups: 1) visual aura associated with MH; 2) visual aura unrelated in time to MH; and 3) visual aura without MH. The frequency of R to L shunt was compared with a control group of 200 patients. Eighty patients underwent PFO closure. Residual shunts, MH, and visual aura were reassessed after 3 and 12 months. RESULTS: The prevalence of R to L shunt in Groups A, B, and C was 96%, 72%, and 67%, respectively, versus 18% in the control group (p < 0.0001). The frequency of shunting was similar in Group B versus Group C, but much higher in all 3 groups compared with control subjects. Twelve months after PFO closure, symptoms of aura were resolved in 52%, 75%, and 80% of patients in Groups A, B, and C, respectively (p = NS). CONCLUSIONS: The similar distribution of R to L shunting in all 3 patient groups and the correlation between PFO closure and improvement of aura suggests a similar pathophysiology between the presence of PFO and the visual aura phenomenon, whether or not headache is present in the symptom complex.