From ejection fraction, to myocardial strain, and myocardial work in echocardiography: Clinical impact and controversies.

Enhancing an echocardiographic tool, aimed to detect even subtle left ventricular (LV) systolic function abnormalities, capable of obtaining both early diagnosis and risk prediction of heart disease, represents an ambitious, attractive, and arduous purpose in the modern era of cardiovascular imaging. Ideally, that tool should be simple, reliable, and reproducible, in order to be concretely applied in routine clinical practice. Importantly, that technique should be physiologically plausible and useful both at the population-level, as well as in the individual subject. For a long time, LV ejection fraction (EF) has been considered the first-line parameter for assessing LV global systolic function, strictly related to the prognosis, at least in some settings. However, LV EF limitations are well-known, even though frequently overemphasized, including its load-dependency. Therefore, myocardial strain techniques have been proposed, deemed able to disclose even subtle early LV function anomalies. Nevertheless, many disadvantages of myocardial strain have been reported as well. More recently, myocardial work (MW) analysis has been introduced as a new echocardiographic tool for the evaluation of LV global systolic function, attempting to overcome EF and strain disadvantages. However, MW has shown many limits as well. Notwithstanding, LV EF still remains a landmark functional classification marker for heart failure and cardiac oncology, allowing reliable fast reassessment of LV function changes during patient management, in order to guide treatment in individual cases as well. Notably, global longitudinal strain and MW parameters seem to show better meaningful results at the population-level, but controversial clinical impact, major limitations, wide cut-offs spread and overlap, when the single value needs to be applied to the single case. Taking into account the recent literature-based evidence, the scope of the present narrative critical review is trying to delineate the different types of information given by the described LV global systolic function parameters, both at the population-level and in the individual case, in order to trace a comparative analysis of advantages and limitations in clinical practice.

Presumed Takotsubo syndrome is associated with high in-hospital mortality in very elderly frail females: a case series.

Given the aging of general population, very elderly females with Takotsubo syndrome (TTS) are not rarely encountered in clinical practice. Although coronary angiography with left ventriculography is the gold standard diagnostic tool to exclude or confirm TTS, currently, this invasive procedure is less frequently performed in older patients with several comorbidities, such as renal failure, anemia, infections, neurological disorders, malignancy, and severe frailty. In these patients, a "presumed" TTS is diagnosed on the basis of clinical presentation, electrocardiogram, cardiac biomarkers, and echocardiographic findings without coronary angiography. While, in younger patients, TTS is generally a benign condition, in very elderly females, it is associated with higher in-hospital mortality and poor prognosis. Herein, we present four cases of ultra-octogenarian females diagnosed with "presumed TTS", who did not undergo coronary angiography due to severe frailty and multiple comorbidities and who exhibited poor outcome. This could arise the question if an early more aggressive approach could have changed final results. Probably, the solution could only be a personalized decision deriving from a profound and detailed discussion of each case through a multidisciplinary team approach.

Ejection fraction at hospital admission stratifies mortality risk in HFmrEF patients aged ≥ 70 years: a retrospective analysis from a tertiary university institution.

BACKGROUND: During the last few years, increasing focus has been placed on heart failure with mildly reduced ejection fraction (HFmrEF), an intermediate phenotype from preserved to reduced ejection fraction (EF). However, clinical features and outcome of HFmrEF in elderly patients aged ≥ 70 yrs have been poorly investigated. METHODS: The present study retrospectively included all consecutive patients aged ≥ 70 yrs discharged from our Institution with a first diagnosis of HFmrEF, between January 2020 and November 2020. All patients underwent transthoracic echocardiography. The primary outcome was all-cause mortality, while the secondary one was the composite of all-cause mortality + rehospitalization for all causes over a mid-term follow-up. RESULTS: The study included 107 HFmrEF patients (84.3 ± 7.4 yrs, 61.7% females). Patients were classified as "old" (70-84 yrs, n = 55) and "oldest-old" (≥ 85 yrs, n = 52) and separately analyzed. As compared to the "oldest-old" patients, the "old" ones were more commonly males (58.2% vs 17.3%, p < 0.001), with history of coronary artery disease (CAD) (54.5% vs 15.4%, p < 0.001) and significantly lower EF (43.5 ± 2.7% vs 47.3 ± 3.6%, p < 0.001) at hospital admission. Mean follow-up was 1.8 ± 1.1 yrs. During follow-up, 29 patients died and 45 were re-hospitalized. Male sex (HR 6.71, 95% CI 1.59-28.4), history of CAD (HR 5.37, 95% CI 2.04-14.1) and EF (HR 0.48, 95% CI 0.34-0.68) were independently associated with all-cause mortality in the whole study population. EF also predicted the composite of all-cause mortality + rehospitalization for all causes. EF < 45% was the best cut-off value to predict both outcomes. CONCLUSIONS: EF at hospital admission is independently associated with all-cause mortality and rehospitalization for all causes in elderly HFmrEF patients over a mid-term follow-up.

The impact of short-term hyperglycemia and obesity on biventricular and biatrial myocardial function assessed by speckle tracking echocardiography in a population of women with gestational diabetes mellitus.

BACKGROUND AND AIMS: To compare biventricular and biatrial myocardial strain indices assessed by two-dimensional speckle tracking echocardiography (2D-STE) in women with gestational diabetes mellitus (GDM) and those with uncomplicated pregnancy at the third trimester of pregnancy and in post-partum. METHODS AND RESULTS: 30 consecutive GDM women and 30 age-, ethnicity- and gestational week-matched controls without any comorbidity were examined in this prospective case-control study. All women underwent obstetric visit, blood tests and transthoracic echocardiography (TTE) implemented with 2D-STE analysis of all cardiac chambers at 36-38 weeks' gestation. TTE and 2D-STE were repeated at 6-10 weeks after delivery. At 36-38 weeks' gestation, GDM women, compared to controls, had significantly higher body mass index (BMI), blood pressure values and inflammatory markers. TTE showed increased left ventricular (LV) mass and impaired LV diastolic function in GDM women, whereas there was no significant difference between the groups in ejection fraction. 2D-STE revealed that biventricular global longitudinal strain (GLS) and biatrial reservoir strain indices were significantly lower in GDM women than controls. Third trimester BMI was inversely correlated with LV-GLS (r = -0.86) and was independently associated with reduced LV-GLS (less negative than -20%) in GDM women in post-partum (OR 1.81, 95%CI 1.14-2.89). A BMI value ≥ 30 kg/m2 had 100% sensitivity and 99.5% specificity for identifying GDM women with impaired LV-GLS in post-partum (AUC = 0.97). CONCLUSION: Women with GDM, compared to women with uncomplicated pregnancy, have significantly lower biventricular and biatrial myocardial deformation indices. These abnormalities may be persistent in post-partum in GDM women with obesity.

Prevalence and clinical outcome of main echocardiographic and hemodynamic heart failure phenotypes in a population of hospitalized patients 70 years old and older.

BACKGROUND: Heart failure (HF) echocardiographic and hemodynamic categories are poorly characterized in the elderly. We aimed to evaluate the prevalence and clinical outcomes of echocardiographic and hemodynamic HF phenotypes in a consecutive series of hospitalized patients aged ≥ 70 years. METHODS: All consecutive patients ≥ 70 years old discharged from the Internal Medicine Unit of our Hospital with a diagnosis of HF, between January and November 2020, entered this retrospective study. All patients underwent physical examination, complete blood tests, chest X-ray and transthoracic echocardiography. At 1-year follow-up, we evaluated the occurrence of the composite outcome of all-cause mortality and re-hospitalization. RESULTS: Two hundred and sixty-one patients (86.3 ± 6.4 years, 60.9% women) were retrospectively analyzed. From the study group, 106 "old" (70-84 years) and 155 "oldest-old" (≥ 85 years) patients were separately analyzed. A total of 169 (64.7%) patients reported the composite outcome during follow-up: 41 (15.7%) died and 128 (49.0%) were re-hospitalized. At 1-year follow-up, survival analysis did not show any statistically significant difference between age groups (p = 0.31) and between HF echocardiographic categories (p = 0.34), whereas HF patients with "cold-dry" phenotype had significantly poorer survival compared to the other hemodynamic subtypes (p < 0.001). Male sex (HR 1.44, 95% CI 1.04-1.98), "cold-dry" phenotype (HR 3.90, 95% CI 1.73-8.77), high sodium level (HR 1.03, 95% CI 1.01-1.04) and low estimated glomerular filtration rate (eGFR) (HR 0.98, 95% CI 0.97-0.99) were independently associated with the outcome occurrence. CONCLUSIONS: Male sex, "cold-dry" phenotype, high sodium level and low eGFR are the main adverse prognostic indicators over a mid-term follow-up in hospitalized patients aged ≥ 70 years.

CHA2DS2-VASc score stratifies mortality risk in heart failure patients aged 75 years and older with and without atrial fibrillation.

BACKGROUND: During the last decade, the CHA2DS2-VASc score has been associated with adverse clinical outcomes in several cardiovascular (CV) and non-cardiovascular diseases beyond atrial fibrillation (AF). Whether the CHA2DS2-VASc score stratifies mortality risk in elderly patients with AF and without AF is not well established. METHODS: All consecutive patients aged ≥ 75 yrs hospitalized due to heart failure (HF), between January 2020 and November 2020, were retrospectively enrolled. All patients underwent physical examination, blood tests, electrocardiography and conventional transthoracic echocardiography. Primary endpoint was all-cause mortality, while secondary endpoint was the composite of all-cause mortality + rehospitalizations for all causes over mid-term follow-up. RESULTS: The study included 261 HF patients (86.3 ± 6.4 years, 60.5% females). 85 AF and 176 non-AF patients were separately analyzed. Compared to non-AF patients, those with AF had significantly higher CHA2DS2-VASc score (5.6 ± 1.4 vs 5.1 ± 1.4, p = 0.007) and lower ejection fraction (47.4 ± 16.5 vs 56.7 ± 15.1%, p < 0.001). Mean follow-up was 1.7 ± 0.5 yrs. During follow-up, 96 patients died (58.3% due to CV causes) and 79 were rehospitalized (58.2% due to CV causes). CHA2DS2-VASc score was independently associated with all-cause mortality in whole study population (HR 1.61, 95% CI 1.36-1.92) and in both AF (HR 1.41, 95% CI 1.09-1.82) and non-AF patients (HR 1.84, 95% CI 1.40-2.40). CHA2DS2-VASc score also predicted the secondary endpoint in the same study groups. CHA2DS2-VASc score ≥ 5 was the best cut-off value for predicting both outcomes. CONCLUSION: At mid-term follow-up, a CHA2DS2-VASc score ≥ 5 predicts increased risk of all-cause mortality and re-hospitalizations for all causes in elderly HF patients, regardless of AF.

Artificial intelligence applied to cardiovascular imaging, a critical focus on echocardiography: The point-of-view from "the other side of the coin".

Cardiovascular imaging has achieved a crucial role in the management of cardiovascular diseases. In this field, echocardiography advantages include wide availability, portability, and affordability, at a relatively low cost. However, echocardiographic assessment requires highly trained operators, and implies high observer variability, as compared with the other cardiac imaging modalities. Hence, artificial intelligence might be extremely helpful. From the point-of-view of the peripheral "Spoke" Hospital potential user ("the other side of the coin"), artificial intelligence development appears very slow in the clinical arena. Many limitations are still present, and require full involvement, cooperation, and coordination of professional operators into Hub-and-Spoke network.

Molecular Approaches and Echocardiographic Deformation Imaging in Detecting Myocardial Fibrosis.

The pathological remodeling of myocardial tissue is the main cause of heart diseases. Several processes are involved in the onset of heart failure, and the comprehension of the mechanisms underlying the pathological phenotype deserves special attention to find novel procedures to identify the site of injury and develop novel strategies, as well as molecular druggable pathways, to counteract the high degree of morbidity associated with it. Myocardial fibrosis (MF) is recognized as a critical trigger for disruption of heart functionality due to the excessive accumulation of extracellular matrix proteins, in response to an injury. Its diagnosis remains focalized on invasive techniques, such as endomyocardial biopsy (EMB), or may be noninvasively detected by cardiac magnetic resonance imaging (CMRI). The detection of MF by non-canonical markers remains a challenge in clinical practice. During the last two decades, two-dimensional (2D) speckle tracking echocardiography (STE) has emerged as a new non-invasive imaging modality, able to detect myocardial tissue abnormalities without specifying the causes of the underlying histopathological changes. In this review, we highlighted the clinical utility of 2D-STE deformation imaging for tissue characterization, and its main technical limitations and criticisms. Moreover, we focalized on the importance of coupling 2D-STE examination with the molecular approaches in the clinical decision-making processes, in particular when the 2D-STE does not reflect myocardial dysfunction directly. We also attempted to examine the roles of epigenetic markers of MF and hypothesized microRNA-based mechanisms aiming to understand how they match with the clinical utility of echocardiographic deformation imaging for tissue characterization and MF assessment.

Influence of chest conformation on ventricular-arterial coupling during normal pregnancy.

PURPOSE: There is still controversy regarding the changes of ventricular-arterial coupling (VAC) during normal pregnancy. The possible influence of chest shape on VAC during normal pregnancy has never been investigated. METHODS: Between October 2019 and June 2020, 59 healthy pregnant women (33.7 ± 4.4 years/old) were consecutively included. They underwent obstetric visit, modified Haller index (MHI) assessment, and complete echocardiographic evaluation with blood pressure measurement to assess arterial elastance (Ea), end-systolic elastance (Ees), and Ea/Ees as an index of VAC, at 12-14 weeks and 36-38 weeks gestation, then 6-9 weeks after delivery. RESULTS: VAC progressively increased from the first to the third trimester of pregnancy, then decreased in the postpartum (P < 0.0001) in the whole study population. Women with concave-shaped chest wall (MHI >2.5, n = 31) but not women with normal chest shape (MHI ≤2.5, n = 28) showed a progressive increase in VAC during normal pregnancy. Women with MHI >2.5 showed a significantly less pronounced increase in stroke volume index (SVi) from the first to the third trimester of pregnancy. There was a strong linear correlation between third trimester MHI and VAC (r = 0.93). CONCLUSIONS: Anatomical and/or extrinsic mechanical factors rather than impaired arterial elastance or reduced left ventricular contractility may contribute to changes in VAC during normal pregnancy in women with concave-shaped chest wall.

An unusual case of painless type A aortic dissection.

The pathogenesis of acute aortic dissection (AAD) is not fully elucidated yet, but it was recently shown that inflammation contributes to the occurrence and development of both Stanford type A and type B AAD. We describe a rare case of a painless type A aortic dissection that occurred in an 85-year-old male, with moderate calcified aortic stenosis and a moderately dilated ascending aorta in 6-month clinical and echocardiographic follow-up. A chronic calculous cholecystitis with neutrophilic leukocytosis and severely increased C reactive protein was diagnosed in the last 3 months. In this patient, a chronic systemic inflammatory state might have contributed to generate the intimal entry tear in the aortic root. In particular, a neutrophil mobilization might have played a causative role in aortic rupture.

Does chest wall conformation influence myocardial strain parameters in infants with pectus excavatum?

PURPOSE: To investigate the possible influence of chest wall conformation on myocardial strain parameters in a consecutive population of infants with pectus excavatum (PE), noninvasively assessed by modified Haller index (MHI). METHODS: Sixteen consecutive PE infants (MHI >2.5) and 44 infants with normal chest shape (MHI ≤2.5) entered in this prospective case-control study. All infants underwent evaluation by neonatologist, transthoracic echocardiography implemented with two-dimensional speckle tracking echocardiography (2D-STE) analysis of both ventricles and MHI assessment (ratio of chest transverse diameter over the distance between sternum and spine), at two time points: within 3 days and at about 40 days of life. RESULTS: At 2.1 ± 1 days of life, compared to controls (MHI = 2.01 ± 0.2), PE infants (MHI = 2.76 ± 0.2) were diagnosed with significantly smaller cardiac chambers dimensions. Biventricular contractile function and hemodynamics were similar in both groups of infants. Left ventricular (LV) global longitudinal strain (GLS) (-16.0 ± 2.8 vs. -21.7 ± 2.2%), LV-global circumferential strain (GCS) (-16.3 ± 2.7 vs. -24.0 ± 5.2%), LV-global radial strain (GRS) (24.2 ± 3.0 vs. 31.5 ± 6.3%), and right ventricular free wall longitudinal strain (RVFWLS) (-16.0 ± 3.2 vs. -22.3 ± 4.4%) were significantly reduced in PE infants versus controls (all p < 0.001). A strong inverse correlation between MHI and the following parameters: LV-GLS (r = -0.92), LV-GCS (r = -0.88), LV-GRS (r = -0.87), and RVFWLS (r = -0.88), was demonstrated in PE infants, but not in controls, in perinatal period (all p < 0.001). Analogous results were obtained at 36.8 ± 5.2 days after birth. CONCLUSIONS: Abnormal chest anatomy progressively impairs myocardial strain parameters in PE infants. This impairment might reflect intraventricular dyssynchrony due to compressive phenomena rather than intrinsic myocardial dysfunction.

Rapid Risk Stratification of Acute Ischemic Stroke Patients in the Emergency Department: The Incremental Prognostic Role of Left Atrial Reservoir Strain.

OBJECTIVES: To determine the prognostic value of positive global left atrial strain (LA-GSA+), measured by two-dimensional speckle tracking echocardiography (2D-STE) in a population of acute ischemic stroke (AIS) patients without atrial fibrillation (AF), in the setting of Emergency Department (ED). METHODS: All consecutive AIS patients with sinus rhythm on ECG and without AF history entered this prospective study. All patients underwent complete blood tests and transthoracic echocardiography implemented with 2D-STE analysis of LA strain parameters within 6-12 h after symptoms onset. At 6-months follow-up, we evaluated the composite endpoint of all-cause mortality plus cardiovascular re-hospitalizations. RESULTS: A total of 102 AIS patients (76.4 ± 10.8 yrs, 47% males) were prospectively included. LA-GSA+ was markedly reduced in AIS patients (20.8 ± 7.7%), without any statistically significant difference between the stroke subtypes. At 6-months follow-up, 7 deaths and 27 re-hospitalizations occurred. On multivariate Cox regression analysis, variables independently associated with outcome were: LA-GSA+ (per unit) (HR 0.29, 95% CI 0.19-0.39) and C-reactive protein (CRP) (per 0.1 mg/dl) (HR 1.45, 95% CI 1.15-1.75) as continuous variables; statin therapy (HR 0.45, 95%CI 0.28-0.62), and type 2 diabetes (HR 1.65, 95% CI 1.15-2.35) as categorical variables. A LA-GSA+ ≤20.0% predicted the occurrence of the above-mentioned outcome at 6-months follow-up with 94% sensitivity and 81% specificity (AUC=0.84). Interestingly, GSA+ showed a strong inverse correlation with CRP levels (r = -0.86). CONCLUSIONS: A LA-GSA+ ≤20% reflects a more advanced atrial cardiomyopathy and might provide a rapid and reliable prognostic risk stratification of AIS patients without AF history in the setting of ED.

Correlation Between Doppler Echocardiography and Right Heart Catheterisation-Derived Systolic and Mean Pulmonary Artery Pressures: Determinants of Discrepancies Between the Two Methods.

BACKGROUND: There is still controversy about whether transthoracic echocardiography (TTE) can provide reliable estimations of pulmonary artery pressures (PAP). The primary endpoint of this study was to evaluate the correlation between TTE and right heart catheterisation (RHC) in estimating systolic (SPAP) and mean (MPAP) pulmonary artery pressures. METHODS: Between January 2011 and December 2018, 141 consecutive patients (average age 63.6±11.5 years; 84 women) with suspected or confirmed pulmonary hypertension (PH) were enrolled into this retrospective observational monocentric study. All patients underwent TTE and, within 3 hours, RHC. The correlation between TTE and RHC in estimating both SPAP and MPAP was retrospectively determined. RESULTS: Seventeen (17) of the patients were excluded due to insufficient TTE signal quality. Of the remaining 124 patients, 18 had no PH. There was moderate correlation between both SPAP and MPAP estimated by TTE and those assessed by RHC (r=0.65 and r=0.60, respectively). Bland-Altman analysis revealed a bias of -11.9 mmHg (with the 95% limits of agreement ranging -45.4 to +21.5 mmHg) for SPAP estimation and -4.6 mmHg (with the 95% limits of agreement ranging -27.9 to +18.8 mmHg) for MPAP estimation, suggesting a general overestimation of PAP by TTE. The main factors responsible for discrepancies between TTE and RHC were: female gender, arrhythmic cardiac electrical activity, systemic arterial hypertension, and diuretic treatment. CONCLUSIONS: Transthoracic echocardiography frequently overestimated PAP in comparison with RHC, especially in hypertensive women with arrhythmias and under diuretic treatment.

False-positive electrocardiographic changes during exercise test in a patient with pectus excavatum.

Exercise-induced ST-segment changes simulating myocardial ischemia have been described in otherwise normal subjects during hyperventilation. We present the case of a 60-year-old man with pectus excavatum showing significant exercise-induced "pseudo-ischaemic" ST-segment changes with neither coronary artery disease nor anxiety-induced hyperventilation. We found no report of the possible causative role of a narrow antero-posterior chest diameter in inducing "pseudo-ischaemic" ST-segment changes during exercise stress test in the literature.

Modes of death and prognostic outliers in chronic heart failure.

BACKGROUND: The impact of incident sudden cardiac death (SCD) on the predictive accuracy of prognostic risk scores for patients with chronic heart failure (HF) has rarely been examined. We assessed the relationship between estimated probability of death and modes of death in this population, as well as the predictors of death and survival in prognostic outliers. METHODS AND RESULTS: The MAGGIC 3-year probability of death was estimated in 6,859 participants of the GISSI-HF trial (mean age 67±11 years, 78% men, 91% with ejection fraction <40%, mean follow-up 3.5±1.3 years, observed mortality 28.4%). The incidence of SCD progressively decreased with increased probability of death, and occurred in 52.5% of patients estimated at low-risk (N = 61 with probability <14%) vs. in 23.5% of the high-risk ones (N = 375 with probability >56%, P < .0001). On the contrary, death from worsening HF was significantly more frequent in the latter group (19.7% vs. 46.1%, P < .0001). The overall predictive accuracy of the MAGGIC model improved after excluding deaths from SCD (AUC from 0.731 to 0.760, P = .0034). Among patients estimated at low-risk (N = 61 dead, 743 alive), independent predictors of death were older age, longer history of HF, higher serum uric acid and chronic obstructive pulmonary disease. The only predictor of survival in patients estimated at high-risk (N = 210 alive, 375 dead) was higher systolic blood pressure. CONCLUSIONS: The MAGGIC risk score demonstrated its scarce ability to capture SCD, particularly in chronic HF patients estimated at low risk of death. Newer and better prognostic tools in the evolving horizon of HF are needed.

AnatoMy and physIopathoLogy of the heArt in a ceNtenarian cOhort (MILANO study).

Background: Centenarians are increasingly being encountered in clinical practice. The aim of the study was to characterize centenarians' clinical features and cardiovascular system. Methods: A prospective, observational, cross-sectional, case-control study included 118 hospitalized >100-year-old patients compared to 50 octogenarians, selected in Milan (Italy) from December 2010 to December 2017, to assess their clinical and echocardiographic characteristics. Results: Centenarians were mostly women with small body surface area; long history of hypertension; chronic renal failure; and low incidence of smoking, diabetes, dyslipidemia, hyperuricemia, coronary artery disease, atrial fibrillation, and cerebrovascular disease. They showed high prevalence of severe cognitive impairment and disability. Almost half of patients (46%) were hospitalized for congestive heart failure (HF), mostly diastolic (80% of cases). Centenarians' hearts had reduced left ventricular end-diastolic dimensions (25.3 ± 3.8 mm/m^2), increased septal thickness (13.3 ± 1.9 mm), and higher relative wall thickness (0.58 ± 0.1). The ejection fraction was usually normal and rarely depressed (57.1% ± 11.7%), whereas the E/e' ratio was considerably increased (17.0 ± 6.0). Noninvasive evaluation of ventricular-arterial coupling parameters revealed significantly higher values of LV end-diastolic elastance in all centenarians versus octogenarians (0.4 ± 01 mm Hg/mL/m^2 vs 0.18 ± 0.2 mm Hg/mL/m^2, P < .0001) and in centenarians with HF versus those without HF (0.5 ± 0.1 mm Hg/mL/m^2 vs 0.34 ± 0.1 mm Hg/mL/m^2, P < .0001). Conclusions: The centenarians' cardiovascular system manifested a significant increase in LV diastolic stiffness with consequent susceptibility to diastolic HF. A progressive afterload increase and a passive load independent mechanism could have contributed to such changes.

Prognostic effects of rosuvastatin in patients with co-existing chronic obstructive pulmonary disease and chronic heart failure: A sub-analysis of GISSI-HF trial.

OBJECTIVES: Rising evidences showed a possible protective role of statins in chronic obstructive pulmonary disease (COPD). We aimed to evaluate in a post-hoc analysis of the GISSI-HF trial the prognostic effect of the use of rosuvastatin in patients with co-existing COPD and HF, assuming that the anti-inflammatory properties of these drugs may imply a potential beneficial effect in these associated chronic inflammatory conditions. METHODS: We analyzed patients with chronic HF and history of COPD deriving from the GISSI-HF study. Of all 4574 patients eligible to statin, 1060 ambulatory patients with HF and concomitant COPD were enrolled and randomly assigned to rosuvastatin 10 mg daily (538 patients) or placebo (522 patients). The primary end-point was to compare all cause death rate in patients randomized to rosuvastatin or placebo. Further, we assessed the effects of rosuvastatin (10 mg daily) on cardiovascular (CV) death, non-CV death and hospital admissions. Median follow-up was 3.9 years with an interquartile range (IQR) of 3.0-4.4. RESULTS: During the follow-up 438 (41.3%) patients died, 304 (28.6%) for CV death and 687 (64.8%) had at least one hospitalization. The two patient groups had similar outcome, irrespective of randomization, in terms of all-cause mortality (log-rank test p = 0.30) CV, non CV-death (p = 0.88 and 0.09 respectively) and all-cause hospitalization (p = 0.82). Cox regression analysis did not show a favorable association between the use of statin and the examined end-points both on unadjusted and adjusted models. CONCLUSIONS: Statin use is not associated with a beneficial effects on all cause, CV, non CV mortality and hospitalization in patients with coexistent chronic HF and history of COPD. ClinicalTrials.gov Identifier: NCT00336336.

Prevalence and Prognostic Impact of Chronic Obstructive Pulmonary Disease in Patients with Chronic Heart Failure: Data from the GISSI-HF Trial.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a common comorbidity in patients with heart failure (HF). We aimed to assess its prevalence, characterization and long-term prognostic impact in the GISSI-HF population. METHODS: The study randomized 6,975 ambulatory HF patients to either n-3 polyunsaturated fatty acids or placebo. We performed a retrospective analysis of clinical characteristics and outcomes of the 1,533 patients diagnosed with COPD (22%). RESULTS: COPD was associated with a worse clinical presentation and an increased burden of comorbidities. At a median follow-up of 3.9 years, COPD was found to be an independent predictor of both predefined primary study end points, including all-cause mortality (HR 1.28, 95% CI 1.15-1.43, p < 0.0001) and all-cause mortality or hospitalization for cardiovascular reasons (HR 1.19, 95% CI 1.10-1.30, p < 0.0001). Both cardiovascular (HR 1.20, 95% CI 1.05-1.36, p = 0.007) and noncardiovascular mortality (HR 1.56, 95% CI 1.26-1.94, p < 0.0001) were significantly increased in COPD-HF patients, as well as hospitalizations for any reason (HR 1.23, 95% CI 1.14-1.34, p < 0.0001), for cardiovascular reasons (HR 1.16, 95% CI 1.06-1.27, p = 0.002) and for HF (HR 1.27, 95% CI 1.14-1.43, p < 0.0001). CONCLUSIONS: COPD is an independent predictor of mortality and hospitalizations in ambulatory HF patients. Increased awareness and improved management of COPD may reduce the burden of this morbidity to patients with HF.