Peak atrial longitudinal strain is predictive of atrial fibrillation in patients with chronic obstructive pulmonary disease and coronary artery disease.

BACKGROUND: The peak atrial longitudinal strain (PALS) has been validated in the prediction of atrial fibrillation (AF) in the general population. If this finding can be applied to patients with chronic obstructive pulmonary disease (COPD) and concomitant coronary artery disease (CAD) is unknown. METHODS AND RESULTS: We analyzed two different study populations of patients with COPD and acute CAD in SCAP trial (Clinical trial.org identifier NCT02324660) and COPD and stable CAD in the NATHAN-NEVER trial (clinical trial.org identifier NCT02519608). All patients enrolled underwent spirometry and clinical specialistic evaluation to test COPD diagnosis. During the index evaluation, all patients underwent echocardiography. The primary endpoint of the study was the occurrence of AF. Overall, 175 patients have been enrolled. PALS was significantly lower in patients with COPD compared to patients without COPD (26% ± 8% vs. 30% ± 8% for PALS4CV, P = .003). After a mean follow-up of 49 ± 15 months, 26 patients experienced at least one episode of AF. At multivariable analysis, only PALS (HR: 0.92, 95% CI: 0.86-0.98, P = .014) resulted as an independent predictor of AF in COPD patients with CAD, with the best cutoff value of 25.5% (sensitivity 87% and specificity 70%). CONCLUSION: The present study confirmed a high incidence of AF events in COPD patients and that PALS is altered and able to independently predict AF in a specific cohort of patients with CAD and COPD. This study points out the need to integrate PALS measurement in the echocardiographic workup of all COPD patients, to early identify those at high risk of AF development.

Transthyretin amyloidosis in aortic stenosis: clinical and therapeutic implications.

About one in seven elderly patients with severe calcific aortic stenosis (AS) also have ATTR amyloid cardiomyopathy (AC-TTR). The reasons for this close association are not fully known, but the two entities are not only related by common epidemiology. For example, it is possible to hypothesize that an amyloidotic infiltration of the aortic valve, even partial, can act as a trigger for the development of endothelial damage and subsequent calcification. Another hypothesis is the increased myocardial strain induced by AS may locally favour the process of amyloidogenesis and tissue infiltration. In a patient with AS, the coexistence of AC-TTR can be suspected by careful analysis of the echocardiogram and the ECG, especially if a clinical history of carpal tunnel syndrome coexists. Bone tracer scintigraphy allows a diagnosis of certainty. Recently, several studies have evaluated the prognostic implications of the coexistence of the two entities in candidates for percutaneous aortic valve replacement, showing how amyloidosis would not significantly impact the results of the procedure, but would only be associated with a greater risk of distant heart failure. In patients with AS associated with AC-TTR, valve replacement should not be ruled out in the presence of the usual clinical-haemodynamic indications.

[Clinical application and limitations of bicycle stress echocardiography (echo-bike)]. / Campi di applicazione e limiti dell'ecocardiografia da sforzo (echo-bike).

Stress echocardiography is an imaging methodology that is widely used in cardiopathic patients for the optimization of diagnosis and prognosis of patients with valvular heart diseases, in defining the response to physical stress in patients with ischemic heart disease, hypertrophic cardiomyopathy, congenital heart disease, or heart failure. However, this method is not yet sufficiently used in clinical practice. Therefore, the aim of this literature review is to describe the main fields of application of stress echocardiography with echo-bike, describing its main advantages and limitations.

Drug-based cardiovascular prevention in patients with Marfan Syndrome: a systematic review.

INTRODUCTION: Marfan Syndrome (MFS) is a rare and complex genetic disorder associated with increased aortic growth and aortic disease. The effectiveness of cardiovascular medical therapies aiming to slow down aortic growth has been tested in several trials, particularly beta-blockers and angiotensin receptor blockers, however showing conflicting results. EVIDENCE ACQUISITION: We conducted a systematic review on PubMed (Medline), Cochrane library, Google Scholar, and Biomed Central databases between January and February 2022. We selected relevant articles focusing on patients with MFS treated with beta-blockers, angiotensin receptors blockers, or both, and reporting data on the effect of the drugs on 1) slowing down aortic dilatation; 2) the reduction of aortic complication (aortic dissection, mortality, aortic surgery); and with a 3) follow-up length of at least two years. A total of 16 studies were selected. EVIDENCE SYNTHESIS: Beta-blockers remain the mainstay of therapy as they have proven to slow aortic enlargement. Angiotensin receptor blockers are a useful alternative and with proven benefit as an add-on therapy to limit aortic growth. Neither beta-blockers, nor angiotensin receptor blockers have shown meaningful results on clinical aortic endpoints. CONCLUSIONS: The current evidence of pharmacological treatment for MFS patients is conflicting due to the lack of large, randomized clinical trials with adequate follow-up studies and homogeneous age grouping. Beta-blockers and angiotensin receptor blockers are the only available treatments to reduce aortic growth. A recently published patient-level meta-analysis confirmed that angiotensin receptor blockers and beta-blockers have a similar effect on reducing the rate of increase of the aortic root Z score, used singularly or as add-on therapy. Considering the current evidence on new features related with MFS (such as mitral annular disjunction - MAD) bearing a potential additional increased arrhythmic risk, it is of paramount importance to establish the role of beta-blockers and angiotensin receptor blockers in clinical endpoints of this population as well.

Cardiopulmonary exercise testing predicts prognosis in amyloid cardiomyopathy: a systematic review and meta-analysis.

BACKGROUND: The clinical value of cardiopulmonary exercise testing (CPET) in cardiac amyloidosis (CA) is uncertain. Due to the growing prevalence of the disease and the current availability of disease-modifying drugs, prognostic stratification is becoming fundamental to optimizing the cost-effectiveness of treatment, patient phenotyping, follow-up, and management. Peak VO2 and VE/VCO2 slope are currently the most studied CPET variables in clinical settings, and both demonstrate substantial, independent prognostic value in several cardiovascular diseases. We aim to study the association of peak VO2 and VE/VCO2 slope with prognosis in patients with CA. METHODS AND RESULTS: We performed a systematic review and searched for clinical studies performing CPET for prognostication in patients with transthyretin-CA and light-chain-CA. Studies reporting hazard ratio (HR) for mortality and peak VO2 or VE/VCO2 slope were further selected for quantitative analysis. HRs were pooled using a random-effect model. Five studies were selected for qualitative and three for quantitative analysis. A total of 233 patients were included in the meta-analysis. Mean peak VO2 resulted consistently depressed, and VE/VCO2 slope was increased. Our pooled analysis showed peak VO2 (pooled HR 0.89, 95% CI 0.84-0.94) and VE/VCO2 slope (pooled HR 1.04, 95% CI 1.01-1.07) were significantly associated with the risk of death in CA patients, with no significant statistical heterogeneity for both analyses. CONCLUSIONS: CPET is a valuable tool for prognostic stratification in CA, identifying patients at increased risk of death. Large prospective clinical trials are needed to confirm this exploratory finding.

Diagnostic pathways to wild-type transthyretin amyloid cardiomyopathy: a multicentre network study.

AIM: Epidemiology of wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) remains poorly defined. A better characterization of pathways leading to ATTRwt-CA diagnosis is of key importance, and potentially informative of disease course and prognosis. The aim of this study was to describe the characteristics of contemporary pathways leading to ATTRwt-CA diagnosis, and their potential association with survival. METHODS AND RESULTS: This was a retrospective study of patients diagnosed with ATTRwt-CA at 17 Italian referral centres for CA. Patients were categorized into different 'pathways' according to the medical reason that triggered the diagnosis of ATTRwt-CA (hypertrophic cardiomyopathy [HCM] pathway, heart failure [HF] pathway, incidental imaging or incidental clinical pathway). Prognosis was investigated with all-cause mortality as endpoint. Overall, 1281 ATTRwt-CA patients were included in the study. The diagnostic pathway leading to ATTRwt-CA diagnosis was HCM in 7% of patients, HF in 51%, incidental imaging in 23%, incidental clinical in 19%. Patients in the HF pathway, as compared to the others, were older and had a greater prevalence of New York Heart Association (NYHA) class III-IV and chronic kidney disease. Survival was significantly worse in the HF versus other pathways, but similar among the three others. In multivariate model, older age at diagnosis, NYHA class III-IV and some comorbidities but not the HF pathway were independently associated with worse survival. CONCLUSIONS: Half of contemporary ATTRwt-CA diagnoses occur in a HF setting. These patients had worse clinical profile and outcome than those diagnosed either due to suspected HCM or incidentally, although prognosis remained primarily related to age, NYHA functional class and comorbidities rather than the diagnostic pathway itself.

The revolution of ATTR amyloidosis in cardiology: certainties, gray zones and perspectives.

Transthyretin (TTR) is a tetrameric protein synthesized mostly by the liver. As a result of gene mutations or as an ageing-related phenomenon, TTR molecules may misfold and deposit in the heart and in other organs as amyloid fibrils. Amyloid transthyretin cardiac amyloidosis (ATTR-CA) manifests typically as left ventricular pseudohypertrophy and/or heart failure with preserved ejection fraction and is an underdiagnosed disorder affecting quality of life and prognosis. This justifies the current search for novel tools for early diagnosis and accurate risk prediction, as well as for safe and effective therapies. In this review we will provide an overview of the main unsolved issues and the most promising research lines on ATTR-CA, ranging from the mechanisms of amyloid formation to therapies.

The role of stress echocardiography in transcatheter aortic valve implantation and transcatheter edge-to-edge repair era: A systematic review.

Objectives: In the last decade, percutaneous treatment of valve disease has changed the approach toward the treatment of aortic stenosis (AS) and mitral regurgitation (MR). The clinical usefulness of stress echocardiography (SE) in the candidates for transcatheter aortic valve implantation (TAVI) and transcatheter edge-to-edge repair (TEER) of MR remains to be established. Therefore, the key aim of this review is to assess the main applications of SE in patients undergoing TAVI or TEER. Methods: We searched for relevant studies to be included in the systematic review on PubMed (Medline), Cochrane library, Google Scholar, and Biomed Central databases. The literature search was conducted in February 2022. The inclusion criteria of the studies were: observational and clinical trials or meta-analysis involving patients with AS or MR evaluated with SE (excluding those in which SE was used only for screening of pseudo-severe stenosis) and treated with percutaneous procedures. Results: Thirteen studies published between 2013 and 2021 were included in the review: five regarding candidates for TEER and eight for TAVI. In TEER candidates, seeing an increase in MR grade, and stroke volume of >40% during SE performed before treatment was, respectively, related to clinical benefits (p = 0.008) and an increased quality of life. Moreover, overall, 25% of patients with moderate secondary MR at rest before TEER had the worsening of MR during SE. At the same time, in SE performed after TEER, an increase in mean transvalvular diastolic gradient and in systolic pulmonary pressure is expected, but without sign and symptoms of heart failure. Regarding TAVI, several studies showed that contractile reserve (CR) is not predictive of post-TAVI ejection fraction recovery and mortality in low-flow low-gradient AS either at 30 days or at long-term. Conclusion: This systematic review shows in TEER candidates, SE has proved useful in the optimization of patient selection and treatment response, while its role in TAVI candidates is less defined. Therefore, larger trials are needed to test and confirm the utility of SE in candidates for percutaneous procedures of valve diseases.

Procalcitonin Predicts Bacterial Infection, but Not Long-Term Occurrence of Adverse Events in Patients with Acute Coronary Syndrome.

This study compiles data to determine if procalcitonin (PCT) values may predict both the risk of bacterial infection and potentially negative long-term outcomes in patients with acute coronary syndromes (ACS). All patients with a diagnosis of ACS that had PCT levels assessed during the first 24 h of hospitalization were enrolled in this study. The primary outcome was to detect the presence of bacterial infection defined as the occurrence of fever and at least one positive blood or urinary culture with clinical signs of infection. The secondary outcome was to monitor the occurrence after 1 year of the composite outcome of all-cause mortality, stroke and myocardial infarction. Overall, 569 patients were enrolled (mean age 69.37 ± 14 years, 30% females). Of these, 44 (8%) met the criteria for bacterial infection. After multivariate analysis, PCT and SBP were found to be independent predictors of bacterial infections (OR for PCT above the cut-off 2.67, 95% CI 1.09-6.53, p = 0.032 and OR for SBP 0.98, 95% CI 0.97-0.99, p = 0.043). After 1 year, the composite outcome of all-cause death, MI and stroke occurred in 104 patients (18%). PCT was not found to be an independent predictor of these outcomes. In conclusion, when assessing ACS, we found that testing for PCT levels during hospital admissions procedures was a good predictor of bacterial infections but not of all-cause mortality, stroke, or myocardial infarction. Clinicaltrial.org identifier: NCT02438085.

Neurological involvement in Ile68Leu (p.Ile88Leu) ATTR amyloidosis: not only a cardiogenic mutation.

BACKGROUND: Ile68Leu transthyretin-related amyloidosis (ATTR) is known as a mainly or exclusively cardiogenic variant. We hypothesized that an accurate specialized neurological evaluation could reveal a consistent frequency of mixed phenotypes. METHODS: Forty-six consecutive subjects with transthyretin (TTR) Ile68Leu (p.Ile88Leu) mutation (29 patients and 17 unaffected carriers) underwent an in-depth cardiac and neurologic evaluation at a single center. RESULTS: All 29 patients showed cardiac involvement. In 20 (69%) cases, it was associated with neurological abnormalities (i.e. a mixed phenotype): 10 (35% of the total) had signs and symptoms of neuropathy, 5 (17%) had abnormalities at the neurologic specialist examination but without symptoms, and 5 (17%) had abnormal nerve conduction study only. None of the asymptomatic carriers showed neurological abnormalities or cardiac involvement. The Neuropathy Impairment Score was > 5 in seven patients at baseline, and became >5 in six more patients during follow-up. The probability of experiencing a major adverse cardiac event (MACE) during follow-up was higher in the mixed than cardiologic phenotype (p = 0.026). Age and phenotype were independent prognostic predictors of MACE. CONCLUSION: At least two-thirds of patients with Ile68Leu ATTR and amyloidotic cardiomyopathy show an associated - definite or probable - neurologic impairment of variable degree if accurately evaluated in a neurologic setting. This proportion can rise during follow-up. The mixed phenotype carries a worse prognosis compared to the exclusively cardiologic one. These observations show that more patients could be eligible for treatment with gene silencers than currently indicated and highlight the need for an in-depth and continuous multidisciplinary evaluation of Ile68Leu ATTR patients.

Contrast Associated Acute Kidney Injury and Mortality in Older Adults with Acute Coronary Syndrome: A Pooled Analysis of the FRASER and HULK Studies.

Whether contrast-associated acute kidney injury (CA-AKI) is only a bystander or a risk factor for mortality in older patients undergoing percutaneous coronary intervention (PCI) is not well understood. Data from FRASER (NCT02386124) and HULK (NCT03021044) studies have been analysed. All patients enrolled underwent coronary angiography. The occurrence of CA-AKI was defined based on KDIGO criteria. The primary outcome of the study was to test the relation between CA-AKI and 3-month mortality. Overall, 870 older ACS adults were included in the analysis (mean age 78 ± 5 years; 28% females). CA-AKI occurred in 136 (16%) patients. At 3 months, 13 (9.6%) patients with CA-AKI died as compared with 13 (1.8%) without it (p < 0.001). At multivariable analysis, CA-AKI emerged as independent predictor of 3-month mortality (HR 3.51, 95%CI 1.05-7.01). After 3 months, renal function returned to the baseline value in 78 (63%) with CA-AKI. Those without recovered renal function (n = 45, 37%) showed an increased risk of mortality as compared to recovered renal function and no CA-AKI subgroups (HR 2.01, 95%CI 1.55-2.59, p = 0.009 and HR 2.71, 95%CI 1.45-5.89, p < 0.001, respectively). In conclusion, CA-AKI occurs in a not negligible portion of older MI patients undergoing invasive strategy and it is associated with short-term mortality.

Phenotypic profile of Ile68Leu transthyretin amyloidosis: an underdiagnosed cause of heart failure.

AIMS: Cardiac amyloidosis remains a great challenge for the cardiologist. One of the three main aetiological forms, transthyretin-related hereditary amyloidosis (ATTRm), can present with several phenotypes, depending mainly on the specific mutation. We aimed to characterize the phenotype of patients with ATTRm due to Ile68Leu mutation, comparing them to patients with wild-type transthyretin amyloidosis (ATTRwt). METHODS AND RESULTS: Data of 67 Ile68Leu ATTRm patients from two Italian referral centres (Bologna and Florence) were retrospectively analysed and compared to those of 82 ATTRwt patients. Fifty-five unaffected mutation carriers were also analysed. Cumulative disease onset was 50% at age 71. A total of 56/67 (84%) patients had a predominantly cardiac phenotype at presentation with concentric increase in left ventricular wall thickness [median 17 mm], and normal or near normal left ventricular ejection fraction (79% of patients). Low QRS voltages were present only in 29% of patients but voltage/mass ratio was low (0.5). Carpal tunnel syndrome was noted in 43%. The overall phenotypic profile was similar to ATTRwt but Ile68Leu ATTRm patients typically presented younger (median 71 vs. 78 years) and were more likely to have (mild) symptomatic neurological involvement (19% vs. 2%). Male prevalence was 44% in unaffected mutation carriers and 78% in affected patients. Age-adjusted survival was comparable between groups. CONCLUSIONS: Ile68Leu ATTRm is a cause of familial amyloidotic cardiomyopathy endemic in central-northern Italy and presents as hypertrophic/restrictive cardiomyopathy quite similar to ATTRwt. Male preponderance is present in affected patients but not in unaffected mutation carriers. Age-adjusted survival is similar to ATTRwt.