The lung water cascade in heart failure.

In heart failure patients, we hypothesize the occurrence of the "lung water cascade," with the various markers hierarchically ranked in a well-defined time sequence: (1) early, proximal hemodynamic event with increase in pulmonary capillary wedge pressure; (2) intermediate, direct imaging sign of pulmonary edema (easily detectable at bedside by lung ultrasound as B-lines); (3) late, distal clinical symptoms and signs such as dyspnea and pulmonary crackles. Completion of the cascade (from hemodynamic to pulmonary to clinical congestion) can require minutes (as with exercise), hours or even weeks (as with impending acute heart failure). Backward rewind of the downhill cascade can be achieved with timely pulmonary decongestion therapy, such as diuretics or dialysis, restoring a relatively dry lung. Any therapeutic intervention is more likely to succeed in the early steps of the cascade, at the imaging stage of asymptomatic pulmonary congestion, rather than downstream near to the end of the cascade, when clinical instability occurred.

Salivary lactate and 8-isoprostaglandin F2α as potential non-invasive biomarkers for monitoring heart failure: a pilot study.

Heart failure (HF) is a cardiovascular disease affecting about 26 million people worldwide costing about $100 billons per year. HF activates several compensatory mechanisms and neurohormonal systems, so we hypothesized that the concomitant monitoring of a panel of potential biomarkers related to such conditions might help predicting HF evolution. Saliva analysis by point-of-care devices is expected to become an innovative and powerful monitoring approach since the chemical composition of saliva mirrors that of blood. The aims of this study were (i) to develop an innovative procedure combining MEPS with UHPLC-MS/MS for the simultaneous determination of 8-isoprostaglandin F2α and cortisol in saliva and (ii) to monitor lactate, uric acid, TNF-α, cortisol, α-amylase and 8-isoprostaglandin F2α concentrations in stimulated saliva samples collected from 44 HF patients during their hospitalisation due to acute HF. Limit of detection of 10 pg/mL, satisfactory recovery (95-110%), and good intra- and inter-day precisions (RSD ≤ 10%) were obtained for 8-isoprostaglandin F2α and cortisol. Salivary lactate and 8-isoprostaglandin F2α were strongly correlated with NT-proBNP. Most patients (about 70%) showed a significant decrease (a factor of 3 at least) of both lactate and 8-isoprostaglandin F2α levels at discharge, suggesting a relationship between salivary levels and improved clinical conditions during hospitalization.

Ultrasound lung comets in systemic sclerosis: a chest sonography hallmark of pulmonary interstitial fibrosis.

OBJECTIVE: To assess the correlation between ultrasound lung comets (ULCs, a recently described echographic sign of interstitial lung fibrosis) and the current undisputed gold-standard high-resolution CT (HRCT) to detect pulmonary fibrosis in patients with SSc. METHODS: We enrolled 33 consecutive SSc patients (mean age 54 +/- 13 years, 30 females) in the Rheumatology Clinic of the University of Pisa. We assessed ULCs and chest HRCT within 1 week independently in all the patients. ULC score was obtained by summing the number of lung comets on the anterior and posterior chest. Pulmonary fibrosis was quantified by HRCT with a previously described 30-point Warrick score. RESULTS: Presence of ULCs (defined as a total number more than 10) was observed in 17 (51%) SSc patients. Mean ULC score was 37 +/- 50, higher in the diffuse than in the limited form (73 +/- 66 vs 21 +/- 35; P < 0.05). A significant positive linear correlation was found between ULCs and Warrick scores (r = 0.72; P < 0.001). CONCLUSIONS: ULCs are often found in SSc, are more frequent in the diffuse than the limited form and are reasonably well correlated with HRCT-derived assessment of lung fibrosis. They represent a simple, bedside, radiation-free hallmark of pulmonary fibrosis of potential diagnostic and prognostic value.

Integrated quadruple stress echocardiography.

Stress echocardiography (SE) is an established diagnostic technique. For 40 years, the cornerstone of the technique has been the detection of regional wall motion abnormalities (RWMA), due to the underlying physiologically-relevant epicardial coronary artery stenosis. In the last decade, three new parameters (more objective than RWMA) have shown the potential to integrate and complement RWMA: 1) B-lines, also known as ultrasound lung comets, as a marker of extravascular lung water, measured using lung ultrasound with the 4-site simplified scan symmetrically of the antero-lateral thorax on the third intercostal space, from mid-axillary to anterior axillary and mid-clavicular line; 2) left ventricular contractile reserve (LVCR), assessed as the peak stress/rest ratio of left ventricular force, also known as elastance (systolic arterial pressure by cuff sphygmomanometer/end-systolic volume from 2D echocardiography); 3) coronary flow velocity reserve (CFVR) on left anterior descending coronary artery, calculated as peak stress/rest ratio of diastolic peak flow velocity assessed using pulsed-wave Doppler. The 4 parameters (RWMA, B-lines, LVCR and CFVR) now converge conceptually, logistically, and methodologically in the Integrated Quadruple (IQ)-SE. IQ-SE optimizes the versatility of SE to include in a one-stop shop the core "ABCD" (asynergy+B-lines+contractile reserve+Doppler flowmetry) protocol. It allows a synoptic assessment of parameters mirroring the epicardial artery stenosis (RWMA), interstitial lung water (B-lines), myocardial function (LVCR) and small coronary vessels (CFVR). Each variable has a clear clinical correlate, different and complementary to all others: RWMA identify an ischemic vs. non-ischemic heart; B-lines a wet vs. dry lung; LVCR a strong vs. weak heart; CFVR a warm vs. cold heart. IQ-SE is highly feasible, with minimal increase in the imaging and analysis time, and obvious diagnostic and prognostic impact also beyond coronary artery disease - especially in heart failure. Large scale effectiveness studies with IQ-SE are now under way with the Stress Echo 2020 Study, and will provide the necessary evidence base prior to large scale acceptance of the technique.