Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease.

Heart failure with preserved ejection fraction (HFpEF) results from a complex interplay of age, genetic, cardiac remodeling, and concomitant comorbidities including hypertension, obesity, diabetes, and chronic kidney disease (CKD). Renal failure is an important comorbidity of HFpEF, as well as a major pathophysiological mechanism for those patients at risk of developing HFpEF. Heart failure (HF) and CKD are intertwined conditions sharing common disease pathways; the so-called "kidney tamponade", explained by an increase in intracapsular pressure caused by fluid retention, is only the latest model to explain renal injury in HF. Recognizing the different phenotypes of HFpEF remains a real challenge; the pathophysiological mechanisms of renal dysfunction may differ across the HF spectrum, as well as the prognostic role. A better understanding of the role of cardiorenal interactions in patients with HF in terms of symptom status, disease progression, and prognosis remains essential in HF management. Historically, patients with HF and CKD have been scarcely represented in clinical trial populations. Current concerns affect the practical approach to HF treatment, and, in this context, physicians are frequently hesitant to prescribe and titrate both new and old treatments. Therefore, the extensive application of HF drugs in diverse HF subtypes with numerous comorbidities and different renal dysfunction etiologies remains a controversial matter of discussion. Numerous recently introduced drugs, such as sodium-glucose-linked transporter 2 inhibitors (SGLT2i), constitute a new therapeutic option for patients with HF and CKD. Because of their protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. The present review delves into the phenotype of patients with HFpEF and CKD from a pathophysiological perspective, proposing a treatment approach that suggests a practical stepwise algorithm for the proper application of life-saving therapies in clinical practice.

Asymptomatic Patients With Brugada ECG Pattern: Long-Term Prognosis From a Large Prospective Study.

BACKGROUND: Brugada syndrome poses significant challenges in terms of risk stratification and management, particularly for asymptomatic patients who comprise the majority of individuals exhibiting Brugada ECG pattern (BrECG). The aim of this study was to evaluate the long-term prognosis of a large cohort of asymptomatic patients with BrECG. METHODS: Asymptomatic patients with BrECG (1149) were consecutively collected from 2 Italian centers and followed-up at least annually for 2 to 22 years. For the 539 asymptomatic patients (men, 433 [80%]; mean age, 46±13 years) with spontaneous type 1 documented on baseline ECG (87%) or 12-lead 24-hour Holter monitoring (13%), an electrophysiologic study (EPS) was proposed; for the 610 patients with drug-induced-only type 1 (men, 420 [69%]; mean age, 44±14 years), multiple ECGs and 12-lead Holter were advised in order to detect the occurrence of a spontaneous type-1 BrECG. Arrhythmic events were defined as sudden death or documented ventricular fibrillation or tachycardia. RESULTS: Median follow-up was 6 (4-9) years. Seventeen (1.5%) arrhythmic events occurred in the overall asymptomatic population (corresponding to an event-rate of 0.2% per year), including 16 of 539 (0.4% per year) in patients with spontaneous type-1 BrECG and 1 of 610 in those with drug-induced type-1 BrECG (0.03% per year; P<0.001). EPS was performed in 339 (63%) patients with spontaneous type-1 BrECG. Patients with spontaneous type-1 BrECG and positive EPS had significantly higher event rates than patients with negative EPS (7 of 103 [0.7% per year] versus 4 of 236 [0.2% per year]; P=0.025). Among 200 patients who declined EPS, 5 events (0.4% per year) occurred. There was 1 device-related death. CONCLUSIONS: The entire population of asymptomatic patients with BrECG exhibits a relatively low event rate per year, which is important in view of the long life expectancy of these young patients. The presence of spontaneous type-1 BrECG associated with positive EPS identifies a subgroup at higher risk. Asymptomatic patients with drug-induced-only BrECG have a minimal arrhythmic risk, but ongoing follow-up with 12-lead Holter monitoring is recommended to detect the appearance of spontaneous type-1 BrECG pattern.

Lifetime Clinical Course of Hypertrophic Cardiomyopathy: Outcome of the Historical Florence Cohort Over 5 Decades.

Background: The current understanding of the clinical course and long-term outcome of patients with hypertrophic cardiomyopathy (HCM) has been extrapolated from cohorts with relatively short follow-up, usually <10 years. Extended assessments more closely reflecting HCM lifetime burden are not available. Objectives: The purpose of this study was to report the lifetime clinical course of HCM. Methods: We analyzed the clinical course of HCM patients diagnosed at our center from 1970 to 1992 and followed annually to the present. Cumulative incidence functions were used to estimate the incidence of HCM-related mortality (including heart failure [HF]/stroke related, sudden cardiac death [SCD]) and non-HCM related. Results: A total of 202 patients (age 41 ± 17 years; 63% male) were followed 27 ± 6 [range: 3-50] years. Overall, 97 (48%) survived and 105 (52%) died during the particularly long follow-up; 69 deaths were related to HCM, including 53 HF related, 11 fatal embolic strokes, and 16 SCDs. Annual overall HCM-related mortality was 1.3%/y, increasing from 0.7% during the first decade to 1.8% in the second/third decade (P < 0.01), mainly driven by increase in HF-/stroke-related events (from 0.6% to 1.3%). The SCD mortality rate was similar in the 2 periods (0.1% vs 0.44%, P = 0.10). Of the 69 HCM deaths, 29 (42%) occurred before the widespread availability of effective contemporary treatment strategies and are considered potentially preventable. Conclusions: In this unique HCM cohort followed for up to 50 years, often before contemporary therapies became widely implemented for HCM, HF frequently progressed over time, while arrhythmic SCD events were less common and remained constant over time. Despite spanning different management eras over 5 decades, HCM-related mortality remained relatively low (1.3%/y).

Myocarditis and Chronic Inflammatory Cardiomyopathy, from Acute Inflammation to Chronic Inflammatory Damage: An Update on Pathophysiology and Diagnosis.

Acute myocarditis covers a wide spectrum of clinical presentations, from uncomplicated myocarditis to severe forms complicated by hemodynamic instability and ventricular arrhythmias; however, all these forms are characterized by acute myocardial inflammation. The term "chronic inflammatory cardiomyopathy" describes a persistent/chronic inflammatory condition with a clinical phenotype of dilated and/or hypokinetic cardiomyopathy associated with symptoms of heart failure and increased risk for arrhythmias. A continuum can be identified between these two conditions. The importance of early diagnosis has grown markedly in the contemporary era with various diagnostic tools available. While cardiac magnetic resonance (CMR) is valid for diagnosis and follow-up, endomyocardial biopsy (EMB) should be considered as a first-line diagnostic modality in all unexplained acute cardiomyopathies complicated by hemodynamic instability and ventricular arrhythmias, considering the local expertise. Genetic counseling should be recommended in those cases where a genotype-phenotype association is suspected, as this has significant implications for patients' and their family members' prognoses. Recognition of the pathophysiological pathway and clinical "red flags" and an early diagnosis may help us understand mechanisms of progression, tailor long-term preventive and therapeutic strategies for this complex disease, and ultimately improve clinical outcomes.

Matching Imaging and Remodulation Effects: Benefits of Cardiac Contractility Modulation Shown by Global Longitudinal Strain: A Case Report.

Cardiac Contractility Modulation (CCM) has been proposed for inpatients affected by heart failure with reduced ejection fraction (HFrEF), with relapsing HF symptoms. We present a case of a patient treated with percutaneous coronary intervention (PCI) in the setting of acute coronary syndrome without persistent ST-segment elevation, with the best medical therapy for decompensated HF. The patient refused the implantable cardioverter-defibrillator (ICD), and to reduce the increasing number of hospitalizations for HF exacerbations, we proposed the use of the cardiac contractility modulation device. After the implant, the patient demonstrated a marked improvement in exercise effort and quality of life (QOL) with a six-minute walk test (SMWT), Minnesota Living with Heart Failure Questionnaire (MLWHFQ), and echocardiographic parameters. At 9 months after discharge, no hospital admissions for HF were recorded. We showed with the speckle tracking imaging how the improvement in global longitudinal strain (GLS) correlates with the remodeling effects on myocardial cells.