Heritable thoracic disease (HTAD) represents a heterogeneous group of genetic conditions predisposing to thoracic aortic aneurysm and dissection, with important implications for patients and families. Accurate diagnosis requires integration of clinical assessment-including subtle syndromic features-and molecular genetic testing, supported by family screening. While aortic root pathology is a hallmark, extra-aortic manifestations such as myocardial dysfunction, arrhythmias, premature atherosclerosis and aneurysms in distal or branch vessels are increasingly recognised, with gene-specific associations informing risk stratification.Imaging plays a central role in diagnosis and longitudinal monitoring. Transthoracic echocardiography remains the first-line tool, but cross-sectional imaging (cardiovascular magnetic resonance or cardiovascular CT) is essential for complete aortic assessment and detection of extra-aortic involvement. Surveillance intervals and imaging techniques must be standardised and tailored to genotype and clinical features.Medical therapy aims to control blood pressure and reduce aortic growth. Beta-blockers and angiotensin receptor blockers are first-line in Marfan syndrome; evidence for other HTAD subtypes is emerging. Surgical thresholds differ by genotype, emphasising the importance of personalised care. Paediatric management follows similar principles but requires adapted imaging techniques, growth-adjusted interpretation and careful timing of intervention.Pregnancy in women with HTAD demands multidisciplinary planning, individualised risk assessment and close follow-up to minimise maternal and fetal complications. Finally, recent data support moderate aerobic activity while avoiding isometric and contact sports; exercise prescriptions should be individualised.Overall, HTAD care requires lifelong, multidisciplinary, gene-informed management, integrating imaging, genetics and lifestyle considerations to optimise outcomes across the lifespan.

Low-renin hypertension (LRH) affects approximately 30 percent of patients with arterial hypertension and represents a spectrum of heterogeneous disorders characterized by low renin levels, increased sodium reabsorption, and expanded circulating volume. LRH includes monogenic and acquired secondary forms; however, the majority of the patients-particularly older individuals and those of African descent-present essential hypertension. Primary aldosteronism is the most frequent secondary cause, marked by excessive and autonomous aldosterone secretion. Other monogenic forms, such as Liddle syndrome, apparent mineralocorticoid excess and familial hyperkalaemic hypertension, are distinguished by specific biochemical and genetic profiles. Acquired causes of LRH include high dietary sodium intake, renal diseases, drugs inhibiting the renin-angiotensin-aldosterone system, and exogenous or endogenous factors like high consumption of mineralocorticoid-like substances (i.e. licorice) or cortisol excess. Careful clinical evaluation, including family history, and measurement of renin, aldosterone, and potassium levels are essential for accurate diagnosis and tailored treatment. Mineralocorticoid receptor activation and/or increased sodium reabsorption are a common mechanism in the pathogenesis of LRH, with a continuum between essential and secondary forms. Recognizing these subtypes has significant therapeutic implications, as targeted treatments can improve long-term outcomes and reduce cardiovascular events. This chapter describes the differential diagnosis and underlying mechanisms of the most common conditions presenting with a LRH phenotype, with a focus on diagnostic and therapeutic approaches.

Cat scratch disease (CSD), caused by Bartonella henselae, is an uncommon cause of fever of unknown origin (FUO) and rarely presents with visceral organ involvement. This case report describes a middle-aged woman with 3 months of night sweats and 1 month of fevers. Initial workup showed elevated inflammatory markers, multiple splenic lesions and a pelvic fluid collection. A detailed history noted that she recently adopted a stray kitten, prompting Bartonella serological testing. Given the atypical presentation, a broad infectious evaluation was also pursued, including testing for mycobacterial, fungal and other bacterial pathogens. When B. henselae IgG titre returned strongly positive and transoesophageal echocardiogram (TEE) showed a tricuspid valve vegetation, the diagnosis of culture-negative endocarditis was established. Treatment with doxycycline and rifampin led to rapid symptom resolution.This case highlights the potential for CSD to present as right-sided endocarditis. Clinicians should consider B. henselae infection in patients with FUO and cat exposure, even without classic regional lymphadenopathy. Due to its fastidious nature, B. henselae often evades culture, underscoring the role of serological or molecular testing in diagnosis. This report emphasises the diagnostic challenges of culture-negative endocarditis and the critical importance of detailed exposure history in guiding targeted diagnostic testing and stepwise serological evaluation in atypical disease patterns.

Clinical and angiographic outcomes following chronic total occlusion (CTO) percutaneous coronary intervention (PCI) remain incompletely investigated, whereas direct comparisons with non-CTO-PCI are missing. The present study aimed to compare the mid-term clinical and angiographic outcomes following successful CTO-PCI and non-CTO-PCI.

Consecutive patients from the Intracoronary Stenting and Angiographic Results - Chronic Total Occlusion (ISAR-CTO) Registry undergoing successful CTO recanalization as well as all successful non-CTO-PCI procedures from our institutional database were included. Propensity score matching (PSM) with a 1:3 matching ratio was performed. The primary endpoint was the incidence of major adverse cardiac events (MACE) at 12-month follow-up. The secondary angiographic endpoint was in-segment binary restenosis at surveillance angiography.

Overall, 453 CTO-PCI patients (472 lesions) and 14733 non-CTO-PCI patients (23458 lesions) were analyzed. After PSM, a total of 1812 patients were included in the present study [CTO-PCI, n=453 patients (472 lesions); non-CTO-PCI, n=1359 patients (1424 lesions)]. There were no significant differences in terms of MACE (adjusted hazard ratio [HR_adj]=1.26, 95% confidence interval [CI] 0.95-1.66) between CTO-PCI and non-CTO-PCI at 12-month follow-up. CTO-PCI independently correlated with a higher risk of target lesion revascularization (TLR) (HR_adj=1.66, 95%CI [1.21-2.27]) and a significantly lower risk of MI (HR_adj=0.231; 95%CI [0.06-0.98]). CTO-PCI independently correlated with the occurrence of binary restenosis (adjusted odds ratio [OR_adj]=1.86, 95%CI [1.38-2.51]) at surveillance angiography.

CTO-PCI was independently associated with significantly higher rates of TLR as well as a significantly lower incidence of MI at 12-months follow-up. QCA analysis of surveillance angiography showed superior angiographic outcomes following non-CTO-PCI.

Pulmonary arterial hypertension (PAH) is a progressive disease associated with significant morbidity and mortality. Combination therapy targeting multiple pathways has been shown to improve clinical outcomes.

The INSPECTIO study was a prospective, multicenter, observational study conducted across 29 Italian centers specializing in PAH management. The study sought to explore the impact of combination therapy on disease progression and quality of life, by assessing non-invasive risk parameters, echocardiographic and hemodynamic conditions, and patient-reported outcomes (PROs). Patients with PAH at low or intermediate mortality risk, treated with macitentan and/or selexipag (as monotherapy or in combination), were enrolled. Data on non-invasive low-risk criteria (WHO Functional Class, 6-min walk distance [6MWD], and NT-proBNP), REVEAL risk scores, echocardiographic and hemodynamic parameters, and patient-reported outcomes (emPHasis-10) were collected at baseline and 12 months. A Narrative Medicine analysis complemented quantitative findings by exploring patients' experiences.

Among 176 patients with follow-up data, the number of non-invasive low-risk criteria increased by an average of 0.15 at 12 months (p = 0.0167). REVEAL 2.0 and REVEAL Lite 2 scores showed significant reductions (mean changes: -1.0, p = 0.0142; -0.8, p = 0.0111, respectively). Modest changes were observed in echocardiographic and hemodynamic parameters. Narrative analysis highlighted strengthened patient-provider relationships and improved coping strategies. Safety outcomes aligned with known profiles.

The INSPECTIO study supports the effectiveness of guideline-directed therapy and regular risk assessment to optimize treatment strategies in PAH. The increase in non-invasive low-risk criteria suggests a stabilization of disease over 12 months.

Atrial fibrillation (AF), a common and clinically significant cardiac rhythm disturbance, is associated with gut microbial dysbiosis. However, the precise role of the microbiota and associated metabolism in this condition remain unclear. Through integrated analysis of clinical cohorts and multiple animal models, we identified an intestinal symbiont, Ruminococcus gnavus (R. gnavus), which suppresses the occurrence of AF and atrial fibrosis by producing the leucine-derived branched-chain fatty acid isovaleric acid (IVA). R. gnavus colonization or exogenous IVA supplementation reduced AF susceptibility and improved fibrosis-driven atrial remodeling. Mechanistically, R. gnavus metabolizes dietary leucine into IVA through its unique enzyme 2-oxoisovalerate ferredoxin reductase γ-subunit (vorC). Microbiome-derived IVA activates G protein-coupled receptor 109A (GPR109A) on atrial cardiomyocytes, inhibiting interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling activation and blocking gasdermin E (GSDME)-mediated pyroptosis through a STAT3-GSDME feedforward circuit. These results reveal that the microbial metabolism of dietary leucine and the production of IVA play pivotal roles in preventing AF onset and progression.

Orthostatic hypotension (OH) is a frequent autonomic feature of Parkinson's disease (PD), yet its long-term clinical consequences remain insufficiently characterized, particularly regarding falls and major vascular events.

Adults aged ≥50 years with PD who had a 2018 hospitalization or outpatient visit and received antiparkinsonian medication were included; the first encounter served as the index. Patients with vascular events in the prior 12 months were excluded. Five-year risks were assessed using inverse probability of treatment weighting (IPTW) and propensity score matching (PSM). Logistic regression estimated ORs, negative binomial models assessed fall counts, and OH pharmacotherapy effects were evaluated.

Among 111,368 patients with PD who met the inclusion criteria, 2598 had OH. OH was independently associated with higher 5-year fall risk (adjusted OR 1.35, 95 % CI 1.21-1.51) and more cumulative falls (IRR 1.22, 95 % CI 1.20-1.24). These associations persisted in PSM analyses. In contrast, OH was not associated with major vascular events (adjusted OR 0.99, 95 % CI 0.86-1.14). Traditional cardiovascular risk factors, including hypertension, dyslipidemia, and diabetes, were strongly associated with vascular outcomes. Among patients with OH, pharmacotherapy was associated with higher fall risk (adjusted OR 1.34, 95 % CI 1.10-1.64) but not with vascular events. Findings were consistent across sensitivity analyses.

In this national PD cohort, both OH and its pharmacotherapy increased long-term fall risk but showed no association with major vascular events. These findings indicate distinct outcome profiles of OH, underscoring the need for focused fall-prevention and further evaluation of vascular safety.

Sepsis, a systemic inflammatory response syndrome caused by infection, can lead to life-threatening multi-organ dysfunction. Among its complications, sepsis-induced cardiomyopathy (SIC) represents one of the most severe conditions with poor prognosis. Currently, pharmacological options for clinical management of SIC are limited and often yield suboptimal outcomes, necessitating the urgent exploration of novel therapeutic strategies. Growth differentiation factor 11 (GDF11), a member of the transforming growth factor-β (TGF-β) superfamily, possesses a variety of biological properties. Importantly, recent studies have highlighted the crucial protective role of GDF11 in various cardiovascular diseases. However, to date, there have been no reports on the alterations and effects of GDF11 in SIC. In this study, we initially observed a significant downregulation of GDF11 expression in both myocardium and serum of C57BL/6 J mice treated with lipopolysaccharide (LPS). Subsequently, through endogenous overexpression of GDF11 or exogenous supplementation with recombinant GDF11, we found that GDF11 mitigated lipid peroxidation-dependent ferroptosis by inhibiting iron accumulation and ameliorating mitochondrial dysfunction, thereby alleviating cardiac dysfunction and myocardial injury in septic mice. Additionally, our cellular experiments demonstrated that GDF11 could also inhibit LPS-induced ferroptosis in neonatal mouse cardiomyocytes. Nevertheless, blocking the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway using ML385 in vivo or Nrf2 siRNA in vitro abrogated the above protective effects of GDF11 against SIC. Taken together, our findings show that GDF11 may alleviate SIC by inhibiting cardiomyocyte ferroptosis through activation of the Nrf2 signaling pathway, suggesting GDF11 as a potential therapeutic target for treating patients with sepsis.

Adipose tissue ATGL has emerged as an important player in cardiovascular disease. Myocardial infarction is accompanied by sympathetic stimulation and activation of white adipose tissue and peripheral lipolysis. We therefore investigate here the role of adipocyte ATGL in a murine model of cardiac ischemia and reperfusion (I/R) by using an inducible, adipocyte specific KO of ATGL (iatATGL-KO). Notably this led to successfully inhibited lipolysis during cardiac ischemia, and KO mice exhibited aggravated cardiac dysfunction and enhanced scar formation after 28 days I/R. This phenotype went along with multiple structural and molecular alterations mainly in the subcutaneous white adipose tissue depot (iWAT) and brown adipose tissue (BAT). The iatATGL-KO mainly reduced BAT activation as well as adiponectin-secretion. In the heart spatial transcriptomic analysis suggested higher mechanical stress in the remote myocardium, which went along with higher oxygen consumption rates (OCR) and higher dependency on glucose as substrate after 24 h I/R. Taken together, iatATGL-KO hearts after I/R seem to be affected in multiple ways, such as a reduction in cardioprotective factors from iWAT and BAT as well as an oxygen wasting effect in the remote zone of the heart, which contribute to the worse outcome. This indicates a time and depot-specific role of adipocyte ATGL in cardiac ischemia and reperfusion injury.

The systems regulating blood pressure and calcium-magnesium (Ca2+-Mg2+) homeostasis are increasingly recognized to have clinically relevant interactions, where alterations in one can lead to significant changes in the other. In this study, we developed a computational model integrating blood pressure regulation and Ca2+-Mg2+ homeostasis in a male rat. We simulated various conditions, including hypertension, Ca2+, Mg2+, and vitamin D3 deficiencies, and primary hyperparathyroidism. Simulations of hypertension, induced by various stimuli like increased renin or aldosterone secretion, demonstrated significant effects on parathyroid hormone (PTH), calcitriol, renal Ca2+/Mg2+ handling, and bone resorption. Dietary Ca2+, Mg2+, and vitamin D3 deficiencies was predicted to elevate mean arterial pressure, with Mg2+ deficiency having a stronger effect. Furthermore, the model predicted that primary hyperparathyroidism elevates PTH, Ca2+, and calcitriol, leading to increased mean arterial pressure and bone loss. Overall, this model provides valuable insights into the mechanistic links between blood pressure regulation and Ca2+-Mg2+ homeostasis, offering insights into clinical conditions like hypertension and hyperparathyroidism.