Heart最新文献

Background: Cancer survivors are at increased risk of heart failure (HF). While cardiotoxicity is commonly sought at the time of cancer chemotherapy, HF develops as a result of multiple 'hits' over time, and there is limited evidence regarding the frequency and causes of HF during survivorship.

Objectives: This systematic review sought to investigate the relationship between cardiotoxic cancer therapies and HF during survivorship.

Methods: We searched the EMBASE, MEDLINE and CINAHL databases for studies reporting HF in adult survivors (≥50 years old), who were ≥5 years postpotential cardiotoxic cancer therapy. A random effects model was used to examine the associations of HF.

Results: Thirteen papers were included, comprising 190 259 participants (mean age 53.5 years, 93% women). The risk of HF was increased (overall RR 1.47 (95% CI (1.17 to 1.86)). Cardiotoxic treatment, compared with cancer alone, provided a similar risk (RR of 1.46 (95% CI 0.98 to 2.16)). The overall HF incidence rate was 2.1% compared with 1.7% in the control arm-an absolute risk difference of 0.4%. In the breast cancer population ratio (11 studies), the overall HF RR was 2.57 (95% CI 1.35 to 4.90)). Although heterogeneity was significant (I²=77.2), this was explained by differences in patient characteristics; once multivariable analysis accounted for follow-up duration (OR 0.99, 95% CI (0.97 to 0.99), p=0.047), age (OR 1.14, 95% CI (1.04 to 1.25), p=0.003) and hypertension (OR 0.95, 95% CI (0.92 to 0.98), p<0.001), residual heterogeneity was low (I²=28.7).

Conclusions: HF is increased in adult cancer survivors, associated with cardiotoxic cancer therapy and standard risk factors. However, the small absolute risk difference between survivors and controls suggests that universal screening of survivors is unjustifiable. A risk model based on age, cardiotoxic cancer therapy and standard risk factors may facilitate a selective screening process in this at-risk population.

Myocardial remodelling, entailing cellular and molecular changes in the different components of the cardiac tissue in response to damage, underlies the morphological and structural changes leading to cardiac remodelling, which in turn contributes to cardiac dysfunction and disease progression. Since cardiac tissue is not available for histomolecular diagnosis, surrogate markers are needed for evaluating myocardial remodelling as part of the clinical management of patients with cardiac disease. In this setting, circulating biomarkers, a component of the liquid biopsy, provide a promising approach for the fast, affordable and scalable screening of large numbers of patients, allowing the detection of different pathological features related to myocardial remodelling, aiding in risk stratification and therapy monitoring. However, despite the advances in the field and the identification of numerous potential candidates, their implementation in clinical practice beyond natriuretic peptides and troponins is mostly lacking. In this review, we will discuss some biomarkers related to alterations in the main cardiac tissue compartments (cardiomyocytes, extracellular matrix, endothelium and immune cells) which have shown potential for the assessment of cardiovascular risk, cardiac remodelling and therapy effects. The hurdles and challenges for their translation into clinical practice will also be addressed.

Background: Young patients suffering from cryptogenic stroke alongside a patent foramen ovale (PFO) are often considered for percutaneous device closure to reduce the risk of stroke recurrence. Residual right-to-left shunt after device closure may persist in approximately a quarter of the patients at 6 months, and some may close at a later time point. This study aimed to assess the prevalence and persistence of residual right-to-left shunt after percutaneous PFO closure.

Methods: Consecutive patients undergoing transoesophageal echocardiography-guided PFO closure for cryptogenic stroke between 2006 and 2021, with echocardiographic follow-up including contrast bubble study and Valsalva manoeuvre, were enrolled. Follow-up transthoracic echocardiography was performed at 6 months and repeated at 12 months in case of residual right-to-left shunt. Primary outcomes included the prevalence and grade of residual right-to-left shunt at 6 and 12 months after percutaneous PFO closure.

Results: 227 patients were included with a mean age of 43±11 years and 50.2% were women. At 6-month follow-up, 72.7% had no residual right-to-left shunt, 12.3% small residual right-to-left shunt, 6.6% moderate residual right-to-left shunt and 8.4% large residual right-to-left shunt. At 12-month follow-up, the presence of residual right-to-left shunt in all patients was 12.3%, of whom 6.6% had small residual right-to-left shunt, 2.6% had moderate residual right-to-left shunt and 3.1% had large residual right-to-left shunt.

Conclusions: Residual right-to-left shunts are common at 6 months after percutaneous closure of PFO. However, the majority are small and two-thirds of residual right-to-left shunts achieve complete closure between 6 and 12 months.

Objective: Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine understanding of the antifibrotic action of spironolactone.

Methods: In this substudy (n=290) to the Heart 'Omics' in Ageing Study trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/day and followed for 9 months. The analysis included 1498 sequenced urinary peptides detectable in ≥30% of patients and carboxyterminal propeptide of procollagen I (PICP) and PICP/carboxyterminal telopeptide of collagen I (CITP) as serum biomarkers of COL1A1 synthesis. After rank normalisation of biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted mixed model analysis of variance. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher's Z transform.

Results: Multivariable-adjusted between-group differences in the urinary peptides with error 1 rate correction were limited to 27 collagen fragments, of which 16 were upregulated (7 COL1A1 fragments) on spironolactone and 11 downregulated (4 COL1A1 fragments). Over 9 months of follow-up, spironolactone decreased serum PICP from 81 (IQR 66-95) to 75 (61-90) µg/L and PICP/CITP from 22 (17-28) to 18 (13-26), whereas no changes occurred in the control group, resulting in a difference (spironolactone minus control) expressed in standardised units of -0.321 (95% CI 0.0007). Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and in PICP or the PICP/CITP ratio.

Conclusions: Spironolactone decreased serum markers of collagen synthesis and predominantly downregulated urinary collagen-derived peptides, but upregulated others. The interpretation of these opposite UPP trends might be due to shrinking the body-wide pool of collagens, explaining downregulation, while some degree of collagen synthesis must be maintained to sustain vital organ functions, explaining upregulation. Combining urinary and serum fibrosis markers opens new avenues for the understanding of the action of antifibrotic drugs.

Trial registration number: NCT02556450.

Background: Treating obesity may be a pathway to prevent and control hypertension. In the SURMOUNT-1 trial in people with obesity or overweight with weight-related complications, 72-week tirzepatide treatment led to clinically meaningful body weight and blood pressure reduction. Post hoc analyses were conducted to further explore the effects of tirzepatide on the pattern of blood pressure reduction and whether the effects were consistent across various subgroups.

Methods: The mixed effect for repeated measure model was used to compare changes in overall blood pressure, across demographic and clinical subgroups, baseline blood pressure subgroups and hypertension categories between SURMOUNT-1 participants randomised to treatment with tirzepatide and placebo. The association between weight changes and blood pressure and adverse events associated with low blood pressure were also evaluated by mediation analysis.

Results: Tirzepatide treatment was associated with a rapid decline in systolic and diastolic blood pressure over the first 24 weeks, followed by blood pressure stabilisation until the end of the observation period, resulting in a significant net reduction by 72 weeks of 6.8 mm Hg systolic and 4.2 mm Hg diastolic blood pressure versus placebo. Participants randomly assigned to any tirzepatide group were more likely than those assigned to placebo to have normal blood pressure at week 72 (58.0% vs 35.2%, respectively). The effects were broadly consistent across baseline blood pressure subgroups, shifting the blood pressure distribution curve to lower blood pressure levels. The mediation analysis indicated that weight loss explained 68% of the systolic and 71% of the diastolic blood pressure reduction. Low blood pressure adverse events were infrequent, but the rate was higher in the tirzepatide group.

Conclusions: In these post hoc analyses, in participants with obesity or overweight, tirzepatide was associated with reduced blood pressure consistently across participant groups primarily via weight loss, with relatively few blood pressure-related adverse events.

Trial registration number: NCT04184622.