In patients with severe aortic stenosis (AS), pulmonary hypertension (PH) typically is indicative of a decompensated disease state with exhausted compensatory mechanisms of the left ventricle, ...meaning a heart failure state resulting from AS-related “cardiac injury”. In the present review article, we discuss new insights into the pathophysiology of AS-induced PH, the prognostic impact, and potential options to prevent and treat PH in this setting. We emphasize recent data from studies focused on invasive hemodynamics in patients with severe AS that are being evaluated for aortic valve replacement, particularly the key relevance of combined pre- and post-capillary PH. This latter represents an advanced form of cardiac injury that is often associated with right ventricular dysfunction and poor prognosis. Given this context, we highlight the relevance of performing right heart catheterization in combination with non-invasive imaging for the comprehensive assessment of AS patients that are being evaluated for aortic valve replacement. Such comprehensive assessment plays a key role not only to precisely define the extent of AS-related cardiac injury but also to distinguish those PH forms that are unrelated to AS.
Nation-wide hospitalization databases include diagnostic information at the level of an entire population over an extended period of time. Comorbidity network and early disease development can be ...unveiled. Chronic obstructive pulmonary disease (COPD) is an underdiagnosed condition for which it is crucial to identify early disease indicators. The identification of gender-specific conditions preceding the onset of COPD may reveal disease progression patterns allowing for early diagnosis and intervention. The objective of the study was to investigate the antecedent hospitalization history of patients newly diagnosed with COPD and to retrace a gender-specific trajectory of coded entities prior to the onset of COPD.
A population-wide hospitalization database including information about all hospitalizations in Switzerland between 2002 and 2018 was used. COPD cases were extracted from the database and comorbidities occurring prior to the onset of COPD identified. Comorbidities significantly over-represented in COPD compared with a 1:1, age- and sex-matched control population were identified and their longitudinal evolution was analyzed.
Between 2002 and 2018, 697,714 hospitalizations with coded COPD were recorded in Switzerland. Sixty-two diagnoses were significantly over-represented before onset of COPD. These preceding comorbidities included both well-established conditions and novel links to COPD. Early pre-conditions included nicotine and alcohol abuse, obesity and cardiovascular diseases. Later comorbidities included atrial fibrillation, diseases of the genitourinary system and pneumonia. Atherosclerotic heart diseases were more prevalent in males, whereas hypothyroidism, varicose and intestinal disorders were more frequent in females. Disease trajectories were validated using an independent data set.
Gender-specific disease trajectories highlight early indicators and pathogenetic links between COPD and antecedent diseases and could allow for early detection and intervention.
Obstructive sleep apnea is an indicator of risk factors predisposing to cardiovascular diseases (i.e., hypertension, diabetes, obesity) and a marker of abnormal cardiac structure and function, and ...observational studies have also suggested that treatment of OSA by continuous positive airway pressure (CPAP) may improve the outcome of patients with OSA and established cardiovascular diseases 2. Similar to other diseases with failure of a “one size fits all” strategy such as heart failure with preserved ejection fraction (HFpEF) 4, a concept of different disease subtypes with different endotypes and phenotypes with different predominant pathophysiological features and therapeutic targets has been put forward 5. ...coronary artery disease is common in OSA and vice versa but the relative contribution of hypertension, diabetes, obesity, and OSA are hard to determine.
Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (T
)1 and T
17 cells. However, mechanisms governing the cardiotoxicity ...programming of heart-specific T cells have remained elusive. Using a mouse model of spontaneous autoimmune myocarditis, we show that progression of myocarditis to lethal heart disease depends on cardiac myosin-specific T
17 cells imprinted in the intestine by a commensal
species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated
specific CD4
T cell and B cell responses observed in human myocarditis patients suggest that mimic peptides from commensal bacteria can promote inflammatory cardiomyopathy in genetically susceptible individuals. The ability to restrain cardiotoxic T cells through manipulation of the microbiome thereby transforms inflammatory cardiomyopathy into a targetable disease.
It is estimated that approximately 50% of the heart failure population has a normal left ventricular ejection fraction, a complex broadly referred to as heart failure with normal left ventricular ...ejection fraction (HFNEF). While these patients have been considered in epidemiologic studies and clinical trials to represent a single pool of patients, limited more detailed studies indicate that HFNEF patients are a very heterogeneous group, with a number of key pathophysiologic mechanisms. This review summarizes and critically analyzes available data on the pathophysiology of HFNEF, placing it into context with a recently developed diagnostic algorithm. We evaluate the utility of commonly applied echocardiographic measures and biomarkers and integrate mechanistic observations into potential future therapeutic directions.
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